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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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The CCAAT-box transcription factor, NF-Y complex, mediates the specification of the IL1 neurons in C. elegans

  • Woojung Heo (Department of Brain Sciences, DGIST) ;
  • Hyeonjeong Hwang (Department of Brain Sciences, DGIST) ;
  • Jimin Kim (Department of Brain Sciences, DGIST) ;
  • Seung Hee Oh (Department of Brain Sciences, DGIST) ;
  • Youngseok Yu (Department of Life and Nanopharmaceutical Sciences, Kyung Hee University) ;
  • Jae-Hyung Lee (Department of Life and Nanopharmaceutical Sciences, Kyung Hee University) ;
  • Kyuhyung Kim (Department of Brain Sciences, DGIST)
  • Received : 2022.09.16
  • Accepted : 2022.10.27
  • Published : 2023.03.31
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Abstract

Neuronal differentiation is highly coordinated through a cascade of gene expression, mediated via interactions between trans-acting transcription factors and cis-regulatory elements of their target genes. However, the mechanisms of transcriptional regulation that determine neuronal cell-fate are not fully understood. Here, we show that the nuclear transcription factor Y (NF-Y) subunit, NFYA-1, is necessary and sufficient to express the flp-3 neuropeptide gene in the IL1 neurons of C. elegans. flp-3 expression is decreased in dorsal and lateral, but not ventral IL1s of nfya-1 mutants. The expression of another terminally differentiated gene, eat-4 vesicular glutamate transporter, is abolished, whereas the unc-8 DEG/ENaC gene and pan-neuronal genes are expressed normally in IL1s of nfya-1 mutants. nfya-1 is expressed in and acts in IL1s to regulate flp-3 and eat-4 expression. Ectopic expression of NFYA-1 drives the expression of flp-3 gene in other cell-types. Promoter analysis of IL1-expressed genes results in the identification of several cis-regulatory motifs which are necessary for IL1 expression, including a putative CCAAT-box located in the flp-3 promoter that NFYA-1 directly interacts with. NFYA-1 and NFYA-2, together with NFYB-1 and NFYC-1, exhibit partly or fully redundant roles in the regulation of flp-3 or unc-8 expression, respectively. Taken together, our data indicate that the NF-Y complex regulates neuronal subtype-specification via regulating a set of terminal-differentiation genes.

Keywords

Acknowledgement

We thank the Caenorhabditis Genetics Center (NIH Office of Research Infrastructure Programs, P40 OD010440) and the National BioResource Project (Japan) for strains. We also thank Jinmahn Kim and Ji-Won Lee for technical supports and K. Kim lab members for helpful comments and discussion on the manuscript. This work was supported by the National Research Foundation of Korea (NRF-2020R1A4A1019436, NRF-2021R1A2C1008418) (K.K.) and (2022R1F1A1071248) (J.L.).

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