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Dot1l interacts with Zc3h10 to activate Ucp1 and other thermogenic genes

Authors :
Danielle Yi
Hai P Nguyen
Jennie Dinh
Jose A Viscarra
Ying Xie
Frances Lin
Madeleine Zhu
Jon M Dempersmier
Yuhui Wang
Hei Sook Sul
Source :
eLife, Vol 9 (2020)
Publication Year :
2020
Publisher :
eLife Sciences Publications Ltd, 2020.

Abstract

Brown adipose tissue is a metabolically beneficial organ capable of dissipating chemical energy into heat, thereby increasing energy expenditure. Here, we identify Dot1l, the only known H3K79 methyltransferase, as an interacting partner of Zc3h10 that transcriptionally activates the Ucp1 promoter and other BAT genes. Through a direct interaction, Dot1l is recruited by Zc3h10 to the promoter regions of thermogenic genes to function as a coactivator by methylating H3K79. We also show that Dot1l is induced during brown fat cell differentiation and by cold exposure and that Dot1l and its H3K79 methyltransferase activity is required for thermogenic gene program. Furthermore, we demonstrate that Dot1l ablation in mice using Ucp1-Cre prevents activation of Ucp1 and other target genes to reduce thermogenic capacity and energy expenditure, promoting adiposity. Hence, Dot1l plays a critical role in the thermogenic program and may present as a future target for obesity therapeutics.

Details

Language :
English
ISSN :
2050084X
Volume :
9
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.8291e8d55a79464fb91118053d19a7ab
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.59990