Molecules and Cells

  • 제46권2호
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  • Pages.86-98
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  • 2023
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Epigenetic Regulations in Mammalian Cells: Roles and Profiling Techniques

  • Uijin Kim (Department of Life Science, University of Seoul) ;
  • Dong-Sung Lee (Department of Life Science, University of Seoul)
  • 투고 : 2023.01.14
  • 심사 : 2023.02.04
  • 발행 : 2023.02.28
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⟨ 이전 논문 다음 논문 ⟩

초록

The genome is almost identical in all the cells of the body. However, the functions and morphologies of each cell are different, and the factors that determine them are the genes and proteins expressed in the cells. Over the past decades, studies on epigenetic information, such as DNA methylation, histone modifications, chromatin accessibility, and chromatin conformation have shown that these properties play a fundamental role in gene regulation. Furthermore, various diseases such as cancer have been found to be associated with epigenetic mechanisms. In this study, we summarized the biological properties of epigenetics and single-cell epigenomic profiling techniques, and discussed future challenges in the field of epigenetics.

키워드

과제정보

This work was supported by the 2021 Research Fund of the University of Seoul.

참고문헌

  1. Angermueller, C., Clark, S.J., Lee, H.J., Macaulay, I.C., Teng, M.J., Hu, T.X., Krueger, F., Smallwood, S.A., Ponting, C.P., and Voet, T. (2016). Parallel single-cell sequencing links transcriptional and epigenetic heterogeneity. Nat. Methods 13, 229-232. https://doi.org/10.1038/nmeth.3728
  2. Arita, K., Isogai, S., Oda, T., Unoki, M., Sugita, K., Sekiyama, N., Kuwata, K., Hamamoto, R., Tochio, H., and Sato, M. (2012). Recognition of modification status on a histone H3 tail by linked histone reader modules of the epigenetic regulator UHRF1. Proc. Natl. Acad. Sci. U. S. A. 109, 12950-12955. https://doi.org/10.1073/pnas.1203701109
  3. Back, F. (1976). The variable condition of euchromatin and heterochromatin. Int. Rev. Cytol. 45, 25-64. https://doi.org/10.1016/S0074-7696(08)60077-7
  4. Ball, M.P., Li, J.B., Gao, Y., Lee, J.H., LeProust, E.M., Park, I.H., Xie, B., Daley, G.Q., and Church, G.M. (2009). Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat. Biotechnol. 27, 361-368. https://doi.org/10.1038/nbt.1533
  5. Banaszynski, L.A., Wen, D., Dewell, S., Whitcomb, S.J., Lin, M., Diaz, N., Elsasser, S.J., Chapgier, A., Goldberg, A.D., and Canaani, E. (2013). Hira-dependent histone H3. 3 deposition facilitates PRC2 recruitment at developmental loci in ES cells. Cell 155, 107-120. https://doi.org/10.1016/j.cell.2013.08.061
  6. Bannister, A.J. and Kouzarides, T. (2011). Regulation of chromatin by histone modifications. Cell Res. 21, 381-395. https://doi.org/10.1038/cr.2011.22
  7. Barski, A., Cuddapah, S., Cui, K., Roh, T.Y., Schones, D.E., Wang, Z., Wei, G., Chepelev, I., and Zhao, K. (2007). High-resolution profiling of histone methylations in the human genome. Cell 129, 823-837. https://doi.org/10.1016/j.cell.2007.05.009
  8. Bartosovic, M., Kabbe, M., and Castelo-Branco, G. (2021). Single-cell CUT&Tag profiles histone modifications and transcription factors in complex tissues. Nat. Biotechnol. 39, 825-835. https://doi.org/10.1038/s41587-021-00869-9
  9. Benton, C.B., Fiskus, W., and Bhalla, K.N. (2017). Targeting histone acetylation: readers and writers in leukemia and cancer. Cancer J. 23, 286-291. https://doi.org/10.1097/PPO.0000000000000284
  10. Bird, A., Taggart, M., Frommer, M., Miller, O.J., and Macleod, D. (1985). A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell 40, 91-99. https://doi.org/10.1016/0092-8674(85)90312-5
  11. Bokar, J.A., Shambaugh, M.E., Polayes, D., Matera, A.G., and Rottman, F.M. (1997). Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA 3, 1233-1247.
  12. Bose, P., Dai, Y., and Grant, S. (2014). Histone deacetylase inhibitor (HDACI) mechanisms of action: emerging insights. Pharmacol. Ther. 143, 323-336. https://doi.org/10.1016/j.pharmthera.2014.04.004
  13. Briggs, S.D., Bryk, M., Strahl, B.D., Cheung, W.L., Davie, J.K., Dent, S.Y., Winston, F., and Allis, C.D. (2001). Histone H3 lysine 4 methylation is mediated by Set1 and required for cell growth and rDNA silencing in Saccharomyces cerevisiae. Genes Dev. 15, 3286-3295. https://doi.org/10.1101/gad.940201
  14. Buenrostro, J.D., Giresi, P.G., Zaba, L.C., Chang, H.Y., and Greenleaf, W.J. (2013). Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213-1218. https://doi.org/10.1038/nmeth.2688
  15. Cao, J., Cusanovich, D.A., Ramani, V., Aghamirzaie, D., Pliner, H.A., Hill, A.J., Daza, R.M., McFaline-Figueroa, J.L., Packer, J.S., and Christiansen, L. (2018). Joint profiling of chromatin accessibility and gene expression in thousands of single cells. Science 361, 1380-1385. https://doi.org/10.1126/science.aau0730
  16. Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R.S., and Zhang, Y. (2002). Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298, 1039-1043. https://doi.org/10.1126/science.1076997
  17. Chen, S., Lake, B.B., and Zhang, K. (2019). High-throughput sequencing of the transcriptome and chromatin accessibility in the same cell. Nat. Biotechnol. 37, 1452-1457. https://doi.org/10.1038/s41587-019-0290-0
  18. Cheow, L.F., Courtois, E.T., Tan, Y., Viswanathan, R., Xing, Q., Tan, R.Z., Tan, D.S., Robson, P., Loh, Y.H., and Quake, S.R. (2016). Single-cell multimodal profiling reveals cellular epigenetic heterogeneity. Nat. Methods 13, 833-836. https://doi.org/10.1038/nmeth.3961
  19. Cheung, W.L., Turner, F.B., Krishnamoorthy, T., Wolner, B., Ahn, S.H., Foley, M., Dorsey, J.A., Peterson, C.L., Berger, S.L., and Allis, C.D. (2005). Phosphorylation of histone H4 serine 1 during DNA damage requires casein kinase II in S. cerevisiae. Curr. Biol. 15, 656-660. https://doi.org/10.1016/j.cub.2005.02.049
  20. Clark, S.J., Argelaguet, R., Kapourani, C.A., Stubbs, T.M., Lee, H.J., AldaCatalinas, C., Krueger, F., Sanguinetti, G., Kelsey, G., and Marioni, J.C. (2018). scNMT-seq enables joint profiling of chromatin accessibility DNA methylation and transcription in single cells. Nat. Commun. 9, 781.
  21. Clayton, A.L., Hebbes, T.R., Thorne, A.W., and Crane-Robinson, C. (1993). Histone acetylation and gene induction in human cells. FEBS Lett. 336, 23-26. https://doi.org/10.1016/0014-5793(93)81601-U
  22. Cokus, S.J., Feng, S., Zhang, X., Chen, Z., Merriman, B., Haudenschild, C.D., Pradhan, S., Nelson, S.F., Pellegrini, M., and Jacobsen, S.E. (2008). Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature 452, 215-219. https://doi.org/10.1038/nature06745
  23. Coulondre, C., Miller, J.H., Farabaugh, P.J., and Gilbert, W. (1978). Molecular basis of base substitution hotspots in Escherichia coli. Nature 274, 775-780. https://doi.org/10.1038/274775a0
  24. Cusanovich, D.A., Daza, R., Adey, A., Pliner, H.A., Christiansen, L., Gunderson, K.L., Steemers, F.J., Trapnell, C., and Shendure, J. (2015). Multiplex single-cell profiling of chromatin accessibility by combinatorial cellular indexing. Science 348, 910-914. https://doi.org/10.1126/science.aab1601
  25. Dai, Z.Y., Jin, S.M., Luo, H.Q., Leng, H.L., and Fang, J.D. (2021). LncRNA HOTAIR regulates anoikis-resistance capacity and spheroid formation of ovarian cancer cells by recruiting EZH2 and influencing H3K27 methylation. Neoplasma 68, 509-518. https://doi.org/10.4149/neo_2021_201112N1212
  26. Dekker, J., Rippe, K., Dekker, M., and Kleckner, N. (2002). Capturing chromosome conformation. Science 295, 1306-1311. https://doi.org/10.1126/science.1067799
  27. Deng, S., Zhang, J., Su, J., Zuo, Z., Zeng, L., Liu, K., Zheng, Y., Huang, X., Bai, R., and Zhuang, L. (2022). RNA m6A regulates transcription via DNA demethylation and chromatin accessibility. Nat. Genet. 54, 1427-1437. https://doi.org/10.1038/s41588-022-01173-1
  28. Dey, S.S., Kester, L., Spanjaard, B., Bienko, M., and Van Oudenaarden, A. (2015). Integrated genome and transcriptome sequencing of the same cell. Nat. Biotechnol. 33, 285-289. https://doi.org/10.1038/nbt.3129
  29. Dhayalan, A., Rajavelu, A., Rathert, P., Tamas, R., Jurkowska, R.Z., Ragozin, S., and Jeltsch, A. (2010). The Dnmt3a PWWP domain reads histone 3 lysine 36 trimethylation and guides DNA methylation. J. Biol. Chem. 285, 26114-26120. https://doi.org/10.1074/jbc.M109.089433
  30. Dixon, J.R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J.S., and Ren, B. (2012). Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376-380. https://doi.org/10.1038/nature11082
  31. Downs, J.A., Allard, S., Jobin-Robitaille, O., Javaheri, A., Auger, A., Bouchard, N., Kron, S.J., Jackson, S.P., and Cote, J. (2004). Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites. Mol. Cell 16, 979-990. https://doi.org/10.1016/j.molcel.2004.12.003
  32. Du, H., Zhao, Y., He, J., Zhang, Y., Xi, H., Liu, M., Ma, J., and Wu, L. (2016). YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nat. Commun. 7, 12626.
  33. Eram, M.S., Bustos, S.P., Lima-Fernandes, E., Siarheyeva, A., Senisterra, G., Hajian, T., Chau, I., Duan, S., Wu, H., and Dombrovski, L. (2014). Trimethylation of histone H3 lysine 36 by human methyltransferase PRDM9 protein. J. Biol. Chem. 289, 12177-12188. https://doi.org/10.1074/jbc.M113.523183
  34. Felsenfeld, G. (2014). A brief history of epigenetics. Cold Spring Harb. Perspect. Biol. 6, a018200.
  35. Flyamer, I.M., Gassler, J., Imakaev, M., Brandao, H.B., Ulianov, S.V., Abdennur, N., Razin, S.V., Mirny, L.A., and Tachibana-Konwalski, K. (2017). Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition. Nature 544, 110-114. https://doi.org/10.1038/nature21711
  36. Frei, A.P., Bava, F.A., Zunder, E.R., Hsieh, E.W., Chen, S.Y., Nolan, G.P., and Gherardini, P.F. (2016). Highly multiplexed simultaneous detection of RNAs and proteins in single cells. Nat. Methods 13, 269-275. https://doi.org/10.1038/nmeth.3742
  37. Fritsch, L., Robin, P., Mathieu, J.R., Souidi, M., Hinaux, H., Rougeulle, C., Harel-Bellan, A., Ameyar-Zazoua, M., and Ait-Si-Ali, S. (2010). A subset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and SETDB1 participate in a multimeric complex. Mol. Cell 37, 46-56. https://doi.org/10.1016/j.molcel.2009.12.017
  38. Fu, Y., Jia, G., Pang, X., Wang, R.N., Wang, X., Li, C.J., Smemo, S., Dai, Q., Bailey, K.A., and Nobrega, M.A. (2013). FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA. Nat. Commun. 4, 1798.
  39. Fuks, F., Burgers, W.A., Brehm, A., Hughes-Davies, L., and Kouzarides, T. (2000). DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nat. Genet. 24, 88-91. https://doi.org/10.1038/71750
  40. Geiman, T.M., Sankpal, U.T., Robertson, A.K., Zhao, Y., Zhao, Y., and Robertson, K.D. (2004). DNMT3B interacts with hSNF2H chromatin remodeling enzyme, HDACs 1 and 2, and components of the histone methylation system. Biochem. Biophys. Res. Commun. 318, 544-555. https://doi.org/10.1016/j.bbrc.2004.04.058
  41. Genshaft, A.S., Li, S., Gallant, C.J., Darmanis, S., Prakadan, S.M., Ziegler, C.G., Lundberg, M., Fredriksson, S., Hong, J., and Regev, A. (2016). Multiplexed, targeted profiling of single-cell proteomes and transcriptomes in a single reaction. Genome Biol. 17, 188.
  42. Gerlach, J., van Buggenum, J.A., Tanis, S.E., Hogeweg, M., Heuts, B.M., Muraro, M.J., Elze, L., Rivello, F., Rakszewska, A., and van Oudenaarden, A. (2019). Combined quantification of intracellular (phospho-) proteins and transcriptomics from fixed single cells. Sci. Rep. 9, 1469.
  43. Guelen, L., Pagie, L., Brasset, E., Meuleman, W., Faza, M.B., Talhout, W., Eussen, B.H., De Klein, A., Wessels, L., and De Laat, W. (2008). Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453, 948-951. https://doi.org/10.1038/nature06947
  44. Guo, H., Zhu, P., Wu, X., Li, X., Wen, L., and Tang, F. (2013). Single-cell methylome landscapes of mouse embryonic stem cells and early embryos analyzed using reduced representation bisulfite sequencing. Genome Res. 23, 2126-2135. https://doi.org/10.1101/gr.161679.113
  45. Guo, X., Wang, L., Li, J., Ding, Z., Xiao, J., Yin, X., He, S., Shi, P., Dong, L., and Li, G. (2015). Structural insight into autoinhibition and histone H3-induced activation of DNMT3A. Nature 517, 640-644. https://doi.org/10.1038/nature13899
  46. Haluskova, J. (2010). Epigenetic studies in human diseases. Folia Biol. (Praha) 56, 83-96.
  47. Han, K.Y., Kim, K.T., Joung, J.G., Son, D.S., Kim, Y.J., Jo, A., Jeon, H.J., Moon, H.S., Yoo, C.E., and Chung, W. (2018). SIDR: simultaneous isolation and parallel sequencing of genomic DNA and total RNA from single cells. Genome Res. 28, 75-87. https://doi.org/10.1101/gr.223263.117
  48. Harada, A., Maehara, K., Handa, T., Arimura, Y., Nogami, J., Hayashi-Takanaka, Y., Shirahige, K., Kurumizaka, H., Kimura, H., and Ohkawa, Y. (2019). A chromatin integration labelling method enables epigenomic profiling with lower input. Nat. Cell Biol. 21, 287-296. https://doi.org/10.1038/s41556-018-0248-3
  49. Heintzman, N.D., Stuart, R.K., Hon, G., Fu, Y., Ching, C.W., Hawkins, R.D., Barrera, L.O., Van Calcar, S., Qu, C., and Ching, K.A. (2007). Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat. Genet. 39, 311-318. https://doi.org/10.1038/ng1966
  50. Helm, M. and Motorin, Y. (2017). Detecting RNA modifications in the epitranscriptome: predict and validate. Nat. Rev. Genet. 18, 275-291. https://doi.org/10.1038/nrg.2016.169
  51. Holliday, R. and Pugh, J.E. (1975). DNA modification mechanisms and gene activity during development: developmental clocks may depend on the enzymic modification of specific bases in repeated DNA sequences. Science 187, 226-232. https://doi.org/10.1126/science.187.4173.226
  52. Hotchkiss, R.D. (1948). The quantitative separation of purines, pyrimidines, an d nucleosides by paper chromatography. J. Biol. Chem. 175, 315-332. https://doi.org/10.1016/S0021-9258(18)57261-6
  53. Hou, Y., Guo, H., Cao, C., Li, X., Hu, B., Zhu, P., Wu, X., Wen, L., Tang, F., and Huang, Y. (2016). Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas. Cell Res. 26, 304-319. https://doi.org/10.1038/cr.2016.23
  54. Howell, C.Y., Bestor, T.H., Ding, F., Latham, K.E., Mertineit, C., Trasler, J.M., and Chaillet, J.R. (2001). Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell 104, 829-838. https://doi.org/10.1016/S0092-8674(01)00280-X
  55. Hu, Y., Huang, K., An, Q., Du, G., Hu, G., Xue, J., Zhu, X., Wang, C.Y., Xue, Z., and Fan, G. (2016). Simultaneous profiling of transcriptome and DNA methylome from a single cell. Genome Biol. 17, 88.
  56. Huang, H., Zhu, Q., Jussila, A., Han, Y., Bintu, B., Kern, C., Conte, M., Zhang, Y., Bianco, S., and Chiariello, A.M. (2021). CTCF mediates dosage-and sequence-context-dependent transcriptional insulation by forming local chromatin domains. Nat. Genet. 53, 1064-1074. https://doi.org/10.1038/s41588-021-00863-6
  57. Huang, Y., Su, R., Sheng, Y., Dong, L., Dong, Z., Xu, H., Ni, T., Zhang, Z.S., Zhang, T., and Li, C. (2019). Small-molecule targeting of oncogenic FTO demethylase in acute myeloid leukemia. Cancer Cell 35, 677-691.e10. https://doi.org/10.1016/j.ccell.2019.03.006
  58. Iacono, G., Dubos, A., Meziane, H., Benevento, M., Habibi, E., Mandoli, A., Riet, F., Selloum, M., Feil, R., Zhou, H., et al. (2018). Increased H3K9 methylation and impaired expression of Protocadherins are associated with the cognitive dysfunctions of the Kleefstra syndrome. Nucleic Acids Res. 46, 4950-4965. https://doi.org/10.1093/nar/gky196
  59. Irizarry, R.A., Ladd-Acosta, C., Wen, B., Wu, Z., Montano, C., Onyango, P., Cui, H., Gabo, K., Rongione, M., and Webster, M. (2009). The human colon cancer methylome shows similar hypo-and hypermethylation at conserved tissue-specific CpG island shores. Nat. Genet. 41, 178-186. https://doi.org/10.1038/ng.298
  60. Ito, S., D'Alessio, A.C., Taranova, O.V., Hong, K., Sowers, L.C., and Zhang, Y. (2010). Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466, 1129-1133. https://doi.org/10.1038/nature09303
  61. Jang, K.H., Heras, C.R., and Lee, G. (2022). m6A in the signal transduction network. Mol. Cells 45, 435-443. https://doi.org/10.14348/molcells.2022.0017
  62. Jenuwein, T. and Allis, C.D. (2001). Translating the histone code. Science 293, 1074-1080. https://doi.org/10.1126/science.1063127
  63. Johnson, A., Li, G., Sikorski, T.W., Buratowski, S., Woodcock, C.L., and Moazed, D. (2009). Reconstitution of heterochromatin-dependent transcriptional gene silencing. Mol. Cell 35, 769-781. https://doi.org/10.1016/j.molcel.2009.07.030
  64. Jones, B., Su, H., Bhat, A., Lei, H., Bajko, J., Hevi, S., Baltus, G.A., Kadam, S., Zhai, H., and Valdez, R. (2008). The histone H3K79 methyltransferase Dot1L is essential for mammalian development and heterochromatin structure. PLoS Genet. 4, e1000190.
  65. Karg, E., Smets, M., Ryan, J., Forne, I., Qin, W., Mulholland, C.B., Kalideris, G., Imhof, A., Bultmann, S., and Leonhardt, H. (2017). Ubiquitome analysis reveals PCNA-associated factor 15 (PAF15) as a specific ubiquitination target of UHRF1 in embryonic stem cells. J. Mol. Biol. 429, 3814-3824. https://doi.org/10.1016/j.jmb.2017.10.014
  66. Kaya-Okur, H.S., Wu, S.J., Codomo, C.A., Pledger, E.S., Bryson, T.D., Henikoff, J.G., Ahmad, K., and Henikoff, S. (2019). CUT&Tag for efficient epigenomic profiling of small samples and single cells. Nat. Commun. 10, 1930.
  67. Kim, M.J., Lee, H.J., Choi, M.Y., Kang, S.S., Kim, Y.S., Shin, J.K., and Choi, W.S. (2021). UHRF1 induces methylation of the TXNIP promoter and downregulates gene expression in cervical cancer. Mol. Cells 44, 146-159. https://doi.org/10.14348/molcells.2021.0001
  68. Kim, T. and Buratowski, S. (2009). Dimethylation of H3K4 by Set1 recruits the Set3 histone deacetylase complex to 5' transcribed regions. Cell 137, 259-272. https://doi.org/10.1016/j.cell.2009.02.045
  69. Kleer, C.G., Cao, Q., Varambally, S., Shen, R., Ota, I., Tomlins, S.A., Ghosh, D., Sewalt, R.G., Otte, A.P., and Hayes, D.F. (2003). EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc. Natl. Acad. Sci. U. S. A. 100, 11606-11611. https://doi.org/10.1073/pnas.1933744100
  70. Klein, C.J., Botuyan, M.V., Wu, Y., Ward, C.J., Nicholson, G.A., Hammans, S., Hojo, K., Yamanishi, H., Karpf, A.R., and Wallace, D.C. (2011). Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat. Genet. 43, 595-600. https://doi.org/10.1038/ng.830
  71. Ko, M., Huang, Y., Jankowska, A.M., Pape, U.J., Tahiliani, M., Bandukwala, H.S., An, J., Lamperti, E.D., Koh, K.P., and Ganetzky, R. (2010). Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature 468, 839-843. https://doi.org/10.1038/nature09586
  72. Kong, S.L., Li, H., Tai, J.A., Courtois, E.T., Poh, H.M., Lau, D.P., Haw, Y.X., Iyer, N.G., Tan, D.S.W., and Prabhakar, S. (2019). Concurrent single-cell RNA and targeted DNA sequencing on an automated platform for comeasurement of genomic and transcriptomic signatures. Clin. Chem. 65, 272-281. https://doi.org/10.1373/clinchem.2018.295717
  73. Kouzarides, T. (2007). Chromatin modifications and their function. Cell 128, 693-705. https://doi.org/10.1016/j.cell.2007.02.005
  74. Ku, W.L., Nakamura, K., Gao, W., Cui, K., Hu, G., Tang, Q., Ni, B., and Zhao, K. (2019). Single-cell chromatin immunocleavage sequencing (scChIC-seq) to profile histone modification. Nat. Methods 16, 323-325. https://doi.org/10.1038/s41592-019-0361-7
  75. Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P., and Reinberg, D. (2002). Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev. 16, 2893-2905. https://doi.org/10.1101/gad.1035902
  76. Lan, F. and Shi, Y. (2009). Epigenetic regulation: methylation of histone and non-histone proteins. Sci. China C Life Sci. 52, 311-322. https://doi.org/10.1007/s11427-009-0054-z
  77. Langemeijer, S., Kuiper, R.P., Berends, M., Knops, R., Aslanyan, M.G., Massop, M., Stevens-Linders, E., van Hoogen, P., van Kessel, A.G., and Raymakers, R.A. (2009). Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat. Genet. 41, 838-842. https://doi.org/10.1038/ng.391
  78. Lee, D.S., Luo, C., Zhou, J., Chandran, S., Rivkin, A., Bartlett, A., Nery, J.R., Fitzpatrick, C., O'Connor, C., and Dixon, J.R. (2019). Simultaneous profiling of 3D genome structure and DNA methylation in single human cells. Nat. Methods 16, 999-1006. https://doi.org/10.1038/s41592-019-0547-z
  79. Lee, D.S., Shin, J.Y., Tonge, P.D., Puri, M.C., Lee, S., Park, H., Lee, W.C., Hussein, S.M., Bleazard, T., and Yun, J.Y. (2014). An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator. Nat. Commun. 5, 5619.
  80. Lee, J., Song, J.H., Park, J.H., Chung, M.Y., Lee, S.H., Jeon, S.B., Park, S.H., Hwang, J.T., and Choi, H.K. (2023). Dnmt1/Tet2-mediated changes in Cmip methylation regulate the development of nonalcoholic fatty liver disease by controlling the Gbp2-Pparγ-CD36 axis. Exp. Mol. Med. 55, 143-157. https://doi.org/10.1038/s12276-022-00919-5
  81. Leonhardt, H., Page, A.W., Weier, H.U., and Bestor, T.H. (1992). A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 71, 865-873. https://doi.org/10.1016/0092-8674(92)90561-P
  82. Li, A., Chen, Y.S., Ping, X.L., Yang, X., Xiao, W., Yang, Y., Sun, H.Y., Zhu, Q., Baidya, P., and Wang, X. (2017). Cytoplasmic m6A reader YTHDF3 promotes mRNA translation. Cell Res. 27, 444-447. https://doi.org/10.1038/cr.2017.10
  83. Li, Y. and Seto, E. (2016). HDACs and HDAC inhibitors in cancer development and therapy. Cold Spring Harb. Perspect. Med. 6, a026831.
  84. Lieberman-Aiden, E., Van Berkum, N.L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B.R., Sabo, P.J., and Dorschner, M.O. (2009). Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326, 289-293. https://doi.org/10.1126/science.1181369
  85. Liu, J., Yue, Y., Han, D., Wang, X., Fu, Y., Zhang, L., Jia, G., Yu, M., Lu, Z., and Deng, X. (2014). A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol. 10, 93-95. https://doi.org/10.1038/nchembio.1432
  86. Liu, L., Liu, C., Quintero, A., Wu, L., Yuan, Y., Wang, M., Cheng, M., Leng, L., Xu, L., and Dong, G. (2019). Deconvolution of single-cell multi-omics layers reveals regulatory heterogeneity. Nat. Commun. 10, 470.
  87. Liu, N. and Pan, T. (2015). RNA epigenetics. Transl. Res. 165, 28-35. https://doi.org/10.1016/j.trsl.2014.04.003
  88. Lund, E., Oldenburg, A.R., and Collas, P. (2014). Enriched domain detector: a program for detection of wide genomic enrichment domains robust against local variations. Nucleic Acids Res. 42, e92.
  89. Luo, C., Liu, H., Xie, F., Armand, E.J., Siletti, K., Bakken, T.E., Fang, R., Doyle, W.I., Stuart, T., and Hodge, R.D. (2022). Single nucleus multi-omics identifies human cortical cell regulatory genome diversity. Cell Genom. 2, 100107.
  90. Ma, J.Z., Yang, F., Zhou, C.C., Liu, F., Yuan, J.H., Wang, F., Wang, T.T., Xu, Q.G., Zhou, W.P., and Sun, S.H. (2017). METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N6-methyladenosine-dependent primary MicroRNA processing. Hepatology 65, 529-543. https://doi.org/10.1002/hep.28885
  91. Macaulay, I.C., Haerty, W., Kumar, P., Li, Y.I., Hu, T.X., Teng, M.J., Goolam, M., Saurat, N., Coupland, P., and Shirley, L.M. (2015). G&T-seq: parallel sequencing of single-cell genomes and transcriptomes. Nat. Methods 12, 519-522. https://doi.org/10.1038/nmeth.3370
  92. Maiti, A. and Drohat, A.C. (2011). Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites. J. Biol. Chem. 286, 35334-35338. https://doi.org/10.1074/jbc.C111.284620
  93. Mateo, L.J., Murphy, S.E., Hafner, A., Cinquini, I.S., Walker, C.A., and Boettiger, A.N. (2019). Visualizing DNA folding and RNA in embryos at single-cell resolution. Nature 568, 49-54. https://doi.org/10.1038/s41586-019-1035-4
  94. Meissner, A., Gnirke, A., Bell, G.W., Ramsahoye, B., Lander, E.S., and Jaenisch, R. (2005). Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis. Nucleic Acids Res. 33, 5868-5877. https://doi.org/10.1093/nar/gki901
  95. Meyer, K.D. (2019). DART-seq: an antibody-free method for global m6A detection. Nat. Methods 16, 1275-1280. https://doi.org/10.1038/s41592-019-0570-0
  96. Mikkelsen, T.S., Ku, M., Jaffe, D.B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T.K., and Koche, R.P. (2007). Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448, 553-560. https://doi.org/10.1038/nature06008
  97. Miller, T., Krogan, N.J., Dover, J., Erdjument-Bromage, H., Tempst, P., Johnston, M., Greenblatt, J.F., and Shilatifard, A. (2001). COMPASS: a complex of proteins associated with a trithorax-related SET domain protein. Proc. Natl. Acad. Sci. U. S. A. 98, 12902-12907. https://doi.org/10.1073/pnas.231473398
  98. Mimitou, E.P., Cheng, A., Montalbano, A., Hao, S., Stoeckius, M., Legut, M., Roush, T., Herrera, A., Papalexi, E., and Ouyang, Z. (2019). Multiplexed detection of proteins, transcriptomes, clonotypes and CRISPR perturbations in single cells. Nat. Methods 16, 409-412. https://doi.org/10.1038/s41592-019-0392-0
  99. Miura, F., Enomoto, Y., Dairiki, R., and Ito, T. (2012). Amplification-free whole-genome bisulfite sequencing by post-bisulfite adaptor tagging. Nucleic Acids Res. 40, e136.
  100. Mohn, F., Weber, M., Rebhan, M., Roloff, T.C., Richter, J., Stadler, M.B., Bibel, M., and Schubeler, D. (2008). Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. Mol. Cell 30, 755-766. https://doi.org/10.1016/j.molcel.2008.05.007
  101. Mumbach, M.R., Rubin, A.J., Flynn, R.A., Dai, C., Khavari, P.A., Greenleaf, W.J., and Chang, H.Y. (2016). HiChIP: efficient and sensitive analysis of protein-directed genome architecture. Nat. Methods 13, 919-922. https://doi.org/10.1038/nmeth.3999
  102. Nagano, T., Lubling, Y., Varnai, C., Dudley, C., Leung, W., Baran, Y., Mendelson Cohen, N., Wingett, S., Fraser, P., and Tanay, A. (2017). Cell-cycle dynamics of chromosomal organization at single-cell resolution. Nature 547, 61-67. https://doi.org/10.1038/nature23001
  103. Nan, X., Ng, H.H., Johnson, C.A., Laherty, C.D., Turner, B.M., Eisenman, R.N., and Bird, A. (1998). Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393, 386-389. https://doi.org/10.1038/30764
  104. Ng, S., Yue, W., Oppermann, U., and Klose, R. (2009). Dynamic protein methylation in chromatin biology. Cell. Mol. Life Sci. 66, 407-422. https://doi.org/10.1007/s00018-008-8303-z
  105. North, J.A., Simon, M., Ferdinand, M.B., Shoffner, M.A., Picking, J.W., Howard, C.J., Mooney, A.M., van Noort, J., Poirier, M.G., and Ottesen, J.J. (2014). Histone H3 phosphorylation near the nucleosome dyad alters chromatin structure. Nucleic Acids Res. 42, 4922-4933. https://doi.org/10.1093/nar/gku150
  106. Okano, M., Bell, D.W., Haber, D.A., and Li, E. (1999). DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247-257. https://doi.org/10.1016/S0092-8674(00)81656-6
  107. Okano, M., Xie, S., and Li, E. (1998). Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat. Genet. 19, 219-220. https://doi.org/10.1038/890
  108. Oki, M., Aihara, H., and Ito, T. (2007). Role of histone phosphorylation in chromatin dynamics and its implications in diseases. Subcell. Biochem. 41, 319-336. https://doi.org/10.1007/1-4020-5466-1_14
  109. Otani, J., Nankumo, T., Arita, K., Inamoto, S., Ariyoshi, M., and Shirakawa, M. (2009). Structural basis for recognition of H3K4 methylation status by the DNA methyltransferase 3A ATRX-DNMT3-DNMT3L domain. EMBO Rep. 10, 1235-1241. https://doi.org/10.1038/embor.2009.218
  110. Pan, X., Hong, X., Li, S., Meng, P., and Xiao, F. (2021). METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating primicroRNA-221-3p maturation in a m6A-dependent manner. Exp. Mol. Med. 53, 91-102. https://doi.org/10.1038/s12276-020-00510-w
  111. Paris, J., Morgan, M., Campos, J., Spencer, G.J., Shmakova, A., Ivanova, I., Mapperley, C., Lawson, H., Wotherspoon, D.A., and Sepulveda, C. (2019). Targeting the RNA m6A reader YTHDF2 selectively compromises cancer stem cells in acute myeloid leukemia. Cell Stem Cell 25, 137-148.e6. https://doi.org/10.1016/j.stem.2019.03.021
  112. Parthun, M. (2007). Hat1: the emerging cellular roles of a type B histone acetyltransferase. Oncogene 26, 5319-5328. https://doi.org/10.1038/sj.onc.1210602
  113. Patil, D.P., Chen, C.K., Pickering, B.F., Chow, A., Jackson, C., Guttman, M., and Jaffrey, S.R. (2016). m6A RNA methylation promotes XIST-mediated transcriptional repression. Nature 537, 369-373. https://doi.org/10.1038/nature19342
  114. Peng, W., Li, J., Chen, R., Gu, Q., Yang, P., Qian, W., Ji, D., Wang, Q., Zhang, Z., and Tang, J. (2019). Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway. J. Exp. Clin. Cancer Res. 38, 393.
  115. Peterson, V.M., Zhang, K.X., Kumar, N., Wong, J., Li, L., Wilson, D.C., Moore, R., McClanahan, T.K., Sadekova, S., and Klappenbach, J.A. (2017). Multiplexed quantification of proteins and transcripts in single cells. Nat. Biotechnol. 35, 936-939. https://doi.org/10.1038/nbt.3973
  116. Ping, X.L., Sun, B.F., Wang, L., Xiao, W., Yang, X., Wang, W.J., Adhikari, S., Shi, Y., Lv, Y., and Chen, Y.S. (2014). Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 24, 177-189. https://doi.org/10.1038/cr.2014.3
  117. Piunti, A. and Shilatifard, A. (2016). Epigenetic balance of gene expression by Polycomb and COMPASS families. Science 352, aad9780.
  118. Pogo, B., Allfrey, V., and Mirsky, A. (1966). RNA synthesis and histone acetylation during the course of gene activation in lymphocytes. Proc. Natl. Acad. Sci. U. S. A. 55, 805-812. https://doi.org/10.1073/pnas.55.4.805
  119. Ponciano-Gomez, A., Martinez-Tovar, A., Vela-Ojeda, J., Olarte-Carrillo, I., Centeno-Cruz, F., and Garrido, E. (2017). Mutations in TET2 and DNMT3A genes are associated with changes in global and gene-specific methylation in acute myeloid leukemia. Tumor Biol. 39, 1010428317732181.
  120. Rea, S., Eisenhaber, F., O'Carroll, D., Strahl, B.D., Sun, Z.W., Schmid, M., Opravil, S., Mechtler, K., Ponting, C.P., and Allis, C.D. (2000). Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406, 593-599. https://doi.org/10.1038/35020506
  121. Reyes, M., Billman, K., Hacohen, N., and Blainey, P.C. (2019). Simultaneous profiling of gene expression and chromatin accessibility in single cells. Adv. Biosyst. 3, 1900065.
  122. Rodriguez-Meira, A., Buck, G., Clark, S.A., Povinelli, B.J., Alcolea, V., Louka, E., McGowan, S., Hamblin, A., Sousos, N., and Barkas, N. (2019). Unravelling intratumoral heterogeneity through high-sensitivity single-cell mutational analysis and parallel RNA sequencing. Mol. Cell 73, 1292-1305.e8. https://doi.org/10.1016/j.molcel.2019.01.009
  123. Rotem, A., Ram, O., Shoresh, N., Sperling, R.A., Goren, A., Weitz, D.A., and Bernstein, B.E. (2015). Single-cell ChIP-seq reveals cell subpopulations defined by chromatin state. Nat. Biotechnol. 33, 1165-1172. https://doi.org/10.1038/nbt.3383
  124. Roth, S.Y., Denu, J.M., and Allis, C.D. (2001). Histone acetyltransferases. Annu. Rev. Biochem. 70, 81-120. https://doi.org/10.1146/annurev.biochem.70.1.81
  125. Rowley, M.J. and Corces, V.G. (2018). Organizational principles of 3D genome architecture. Nat. Rev. Genet. 19, 789-800. https://doi.org/10.1038/s41576-018-0060-8
  126. Russler-Germain, D.A., Spencer, D.H., Young, M.A., Lamprecht, T.L., Miller, C.A., Fulton, R., Meyer, M.R., Erdmann-Gilmore, P., Townsend, R.R., and Wilson, R.K. (2014). The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers. Cancer Cell 25, 442-454. https://doi.org/10.1016/j.ccr.2014.02.010
  127. Santos-Rosa, H., Schneider, R., Bannister, A.J., Sherriff, J., Bernstein, B.E., Emre, N., Schreiber, S.L., Mellor, J., and Kouzarides, T. (2002). Active genes are tri-methylated at K4 of histone H3. Nature 419, 407-411. https://doi.org/10.1038/nature01080
  128. Satpathy, A.T., Saligrama, N., Buenrostro, J.D., Wei, Y., Wu, B., Rubin, A.J., Granja, J.M., Lareau, C.A., Li, R., and Qi, Y. (2018). Transcript-indexed ATAC-seq for precision immune profiling. Nat. Med. 24, 580-590. https://doi.org/10.1038/s41591-018-0008-8
  129. Saxonov, S., Berg, P., and Brutlag, D.L. (2006). A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc. Natl. Acad. Sci. U. S. A. 103, 1412-1417. https://doi.org/10.1073/pnas.0510310103
  130. Schoenfelder, S. and Fraser, P. (2019). Long-range enhancer-promoter contacts in gene expression control. Nat. Rev. Genet. 20, 437-455. https://doi.org/10.1038/s41576-019-0128-0
  131. Schuhmacher, M.K., Kudithipudi, S., Kusevic, D., Weirich, S., and Jeltsch, A. (2015). Activity and specificity of the human SUV39H2 protein lysine methyltransferase. Biochim. Biophys. Acta 1849, 55-63. https://doi.org/10.1016/j.bbagrm.2014.11.005
  132. Shahi, P., Kim, S.C., Haliburton, J.R., Gartner, Z.J., and Abate, A.R. (2017). Abseq: ultrahigh-throughput single cell protein profiling with droplet microfluidic barcoding. Sci. Rep. 7, 44447.
  133. Skene, P.J. and Henikoff, S. (2017). An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites. Elife 6, e21856.
  134. Smallwood, S.A., Lee, H.J., Angermueller, C., Krueger, F., Saadeh, H., Peat, J., Andrews, S.R., Stegle, O., Reik, W., and Kelsey, G. (2014). Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity. Nat. Methods 11, 817-820. https://doi.org/10.1038/nmeth.3035
  135. Smith, Z.D. and Meissner, A. (2013). DNA methylation: roles in mammalian development. Nat. Rev. Genet. 14, 204-220. https://doi.org/10.1038/nrg3354
  136. Song, L. and Crawford, G.E. (2010). DNase-seq: a high-resolution technique for mapping active gene regulatory elements across the genome from mammalian cells. Cold Spring Harb. Protoc. 2010, pdb. prot5384.
  137. Spellmon, N., Holcomb, J., Trescott, L., Sirinupong, N., and Yang, Z. (2015). Structure and function of SET and MYND domain-containing proteins. Int. J. Mol. Sci. 16, 1406-1428. https://doi.org/10.3390/ijms16011406
  138. Spencer, D.H., Russler-Germain, D.A., Ketkar, S., Helton, N.M., Lamprecht, T.L., Fulton, R.S., Fronick, C.C., O'Laughlin, M., Heath, S.E., and Shinawi, M. (2017). CpG island hypermethylation mediated by DNMT3A is a consequence of AML progression. Cell 168, 801-816.e13. https://doi.org/10.1016/j.cell.2017.01.021
  139. Stevens, T.J., Lando, D., Basu, S., Atkinson, L.P., Cao, Y., Lee, S.F., Leeb, M., Wohlfahrt, K.J., Boucher, W., and O'Shaughnessy-Kirwan, A. (2017). 3D structures of individual mammalian genomes studied by single-cell Hi-C. Nature 544, 59-64. https://doi.org/10.1038/nature21429
  140. Stoeckius, M., Hafemeister, C., Stephenson, W., Houck-Loomis, B., Chattopadhyay, P.K., Swerdlow, H., Satija, R., and Smibert, P. (2017). Simultaneous epitope and transcriptome measurement in single cells. Nat. Methods 14, 865-868. https://doi.org/10.1038/nmeth.4380
  141. Strahl, B.D. and Allis, C.D. (2000). The language of covalent histone modifications. Nature 403, 41-45. https://doi.org/10.1038/47412
  142. Suraweera, A., O'Byrne, K.J., and Richard, D.J. (2018). Combination therapy with histone deacetylase inhibitors (HDACi) for the treatment of cancer: achieving the full therapeutic potential of HDACi. Front. Oncol. 8, 92.
  143. Szabo, Q., Donjon, A., Jerkovic, I., Papadopoulos, G.L., Cheutin, T., Bonev, B., Nora, E.P., Bruneau, B.G., Bantignies, F., and Cavalli, G. (2020). Regulation of single-cell genome organization into TADs and chromatin nanodomains. Nat. Genet. 52, 1151-1157. https://doi.org/10.1038/s41588-020-00716-8
  144. Tachibana, M., Sugimoto, K., Nozaki, M., Ueda, J., Ohta, T., Ohki, M., Fukuda, M., Takeda, N., Niida, H., and Kato, H. (2002). G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev. 16, 1779-1791. https://doi.org/10.1101/gad.989402
  145. Tahiliani, M., Koh, K.P., Shen, Y., Pastor, W.A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L.M., Liu, D.R., and Aravind, L. (2009). Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324, 930-935. https://doi.org/10.1126/science.1170116
  146. Waddington, C.H. (1942). The epigenotype. Endeavour 1, 18-20.
  147. Wang, X., Zhao, B.S., Roundtree, I.A., Lu, Z., Han, D., Ma, H., Weng, X., Chen, K., Shi, H., and He, C. (2015). N6-methyladenosine modulates messenger RNA translation efficiency. Cell 161, 1388-1399. https://doi.org/10.1016/j.cell.2015.05.014
  148. Wang, Y., Yuan, P., Yan, Z., Yang, M., Huo, Y., Nie, Y., Zhu, X., Qiao, J., and Yan, L. (2021). Single-cell multiomics sequencing reveals the functional regulatory landscape of early embryos. Nat. Commun. 12, 1247.
  149. Weber, A.R., Krawczyk, C., Robertson, A.B., Kusnierczyk, A., Vagbo, C.B., Schuermann, D., Klungland, A., and Schar, P. (2016). Biochemical reconstitution of TET1-TDG-BER-dependent active DNA demethylation reveals a highly coordinated mechanism. Nat. Commun. 7, 10806.
  150. Weber, M., Davies, J.J., Wittig, D., Oakeley, E.J., Haase, M., Lam, W.L., and Schuebeler, D. (2005). Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat. Genet. 37, 853-862. https://doi.org/10.1038/ng1598
  151. Wei, C.L., Wu, Q., Vega, V.B., Chiu, K.P., Ng, P., Zhang, T., Shahab, A., Yong, H.C., Fu, Y., and Weng, Z. (2006). A global map of p53 transcription-factor binding sites in the human genome. Cell 124, 207-219. https://doi.org/10.1016/j.cell.2005.10.043
  152. Wei, Y., Mizzen, C.A., Cook, R.G., Gorovsky, M.A., and Allis, C.D. (1998). Phosphorylation of histone H3 at serine 10 is correlated with chromosome condensation during mitosis and meiosis in Tetrahymena. Proc. Natl. Acad. Sci. U. S. A. 95, 7480-7484. https://doi.org/10.1073/pnas.95.13.7480
  153. Xu, Z., Lee, D.S., Chandran, S., Le, V.T., Bump, R., Yasis, J., Dallarda, S., Marcotte, S., Clock, B., and Haghani, N. (2022). Structural variants drive context-dependent oncogene activation in cancer. Nature 612, 564-572. https://doi.org/10.1038/s41586-022-05504-4
  154. Yan, R., Gu, C., You, D., Huang, Z., Qian, J., Yang, Q., Cheng, X., Zhang, L., Wang, H., and Wang, P. (2021). Decoding dynamic epigenetic landscapes in human oocytes using single-cell multi-omics sequencing. Cell Stem Cell 28, 1641-1656.e7. https://doi.org/10.1016/j.stem.2021.04.012
  155. Yang, X.J. and Seto, E. (2008). Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol. Cell 31, 449-461. https://doi.org/10.1016/j.molcel.2008.07.002
  156. Yuan, W., Xu, M., Huang, C., Liu, N., Chen, S., and Zhu, B. (2011). H3K36 methylation antagonizes PRC2-mediated H3K27 methylation. J. Biol. Chem. 286, 7983-7989. https://doi.org/10.1074/jbc.M110.194027
  157. Zaidi, S., Choi, M., Wakimoto, H., Ma, L., Jiang, J., Overton, J.D., Romano-Adesman, A., Bjornson, R.D., Breitbart, R.E., and Brown, K.K. (2013). De novo mutations in histone-modifying genes in congenital heart disease. Nature 498, 220-223. https://doi.org/10.1038/nature12141
  158. Zhang, C., Samanta, D., Lu, H., Bullen, J.W., Zhang, H., Chen, I., He, X., and Semenza, G.L. (2016). Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA. Proc. Natl. Acad. Sci. U. S. A. 113, E2047-E2056.
  159. Zhang, Z., Theler, D., Kaminska, K.H., Hiller, M., de la Grange, P., Pudimat, R., Rafalska, I., Heinrich, B., Bujnicki, J.M., and Allain, F.H.T. (2010). The YTH domain is a novel RNA binding domain. J. Biol. Chem. 285, 14701-14710. https://doi.org/10.1074/jbc.M110.104711
  160. Zhao, J., Li, B., Ren, Y., Liang, T., Wang, J., Zhai, S., Zhang, X., Zhou, P., Zhang, X., and Pan, Y. (2021). Histone demethylase KDM4A plays an oncogenic role in nasopharyngeal carcinoma by promoting cell migration and invasion. Exp. Mol. Med. 53, 1207-1217. https://doi.org/10.1038/s12276-021-00657-0
  161. Zheng, G., Dahl, J.A., Niu, Y., Fedorcsak, P., Huang, C.M., Li, C.J., Vagbo, C.B., Shi, Y., Wang, W.L., and Song, S.H. (2013). ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell 49, 18-29. https://doi.org/10.1016/j.molcel.2012.10.015
  162. Zhu, C., Yu, M., Huang, H., Juric, I., Abnousi, A., Hu, R., Lucero, J., Behrens, M.M., Hu, M., and Ren, B. (2019). An ultra high-throughput method for single-cell joint analysis of open chromatin and transcriptome. Nat. Struct. Mol. Biol. 26, 1063-1070. https://doi.org/10.1038/s41594-019-0323-x