Animal Bioscience

Asian Australasian Association of Animal Production Societies (아세아태평양축산학회)
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DOT1-like histone lysine methyltransferase is critical for adult vessel maintenance and functions

  • HeeJi Lee (Department of Stem Cell and Regenerative Biotechnology, Institute of Advanced Regenerative Science, Konkuk University) ;
  • Dong Wook Han (Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, Wuyi University) ;
  • Hyeonwoo La (Department of Stem Cell and Regenerative Biotechnology, Institute of Advanced Regenerative Science, Konkuk University) ;
  • Chanhyeok Park (Department of Stem Cell and Regenerative Biotechnology, Institute of Advanced Regenerative Science, Konkuk University) ;
  • Kiye Kang (Department of Stem Cell and Regenerative Biotechnology, Institute of Advanced Regenerative Science, Konkuk University) ;
  • Ohbeom Kwon (Department of Stem Cell and Regenerative Biotechnology, Institute of Advanced Regenerative Science, Konkuk University) ;
  • Sang Jun Uhm (Department of Animal Science, Sangji University) ;
  • Hyuk Song (Department of Stem Cell and Regenerative Biotechnology, Institute of Advanced Regenerative Science, Konkuk University) ;
  • Jeong Tae Do (Department of Stem Cell and Regenerative Biotechnology, Institute of Advanced Regenerative Science, Konkuk University) ;
  • Youngsok Choi (Department of Stem Cell and Regenerative Biotechnology, Institute of Advanced Regenerative Science, Konkuk University) ;
  • Kwonho Hong (Department of Stem Cell and Regenerative Biotechnology, Institute of Advanced Regenerative Science, Konkuk University)
  • Received : 2023.10.06
  • Accepted : 2024.02.16
  • Published : 2024.09.01
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Abstract

Objective: Disruptor of telomeric silencing 1-like (DOT1L) is the only known histone H3K79 methyltransferase essential for the development of the embryonic cardiovascular system, including the heart, blood vessels, and lymphatic vessels, through transcriptional regulation. Our previous study demonstrated that Dot1l deletion results in aberrant lymphatic development and function. However, its precise function in the postnatal cardiovascular system remains unknown. Methods: Using conditional and inducible Dot1l knockout (KO) mice, along with a reporter strain carrying the Geo gene at the Dot1l locus, DOT1L expression and its function in the vascular system during postnatal life were investigated. To assess vessel morphology and vascular permeability, we administered Latex or Evans blue dye to KO mice. In addition, in vitro tube formation and cell migration assays were performed using DOT1L-depleted human umbilical vein endothelial cells (HUVECs). Changes in the expression of vascular genes in HUVECs were measured by quantitative polymerase chain reaction. Results: Our findings demonstrate that conditional Dot1l knockout in the Tg (Tie2-cre) strain results in abnormal blood vessel formation and lymphatic anomalies in the intestine. In a mouse model of Rosa26-creER-mediated inducible Dot1l knockout, we observed vascular phenotypes, including increased vascular permeability and brain hemorrhage, when DOT1L was deleted in adulthood. Additionally, DOT1L depletion in cultured HUVECs led to impaired cell migration and tube formation, likely due to altered gene transcription. These findings highlight the essential role of DOT1L in maintaining vascular integrity and function during embryonic development and postnatal life. Conclusion: Our study revealed that DOT1L is required for the maintenance of adult vascular function through the regulation of gene expression.

Keywords

Acknowledgement

The authors are indebted to all the members of the KH lab for helpful discussion.

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