Abstract

In acute cold stress in mammals, JMJD1A, a histone H3 lysine 9 (H3K9) demethylase, upregulates thermogenic gene expressions through β-adrenergic signaling in brown adipose tissue (BAT). Aside BAT-driven thermogenesis, mammals have another mechanism to cope with long-term cold stress by inducing the browning of the subcutaneous white adipose tissue (scWAT). Here, we show that this occurs through a two-step process that requires both β-adrenergic-dependent phosphorylation of S265 and demethylation of H3K9me2 by JMJD1A. The histone demethylation-independent acute Ucp1 induction in BAT and demethylation-dependent chronic Ucp1 expression in beige scWAT provides complementary molecular mechanisms to ensure an ordered transition between acute and chronic adaptation to cold stress. JMJD1A mediates two major signaling pathways, namely, β-adrenergic receptor and peroxisome proliferator-activated receptor-γ (PPARγ) activation, via PRDM16-PPARγ-P-JMJD1A complex for beige adipogenesis. S265 phosphorylation of JMJD1A, and the following demethylation of H3K9me2 might prove to be a novel molecular target for the treatment of metabolic disorders, via promoting beige adipogenesis.

Details

Title
Histone demethylase JMJD1A coordinates acute and chronic adaptation to cold stress via thermogenic phospho-switch
Author
Abe, Yohei 1 ; Fujiwara, Yosuke 1 ; Takahashi, Hiroki 1 ; Matsumura, Yoshihiro 1 ; Sawada, Tomonobu 1 ; Jiang, Shuying 2 ; Nakaki, Ryo 3 ; Uchida, Aoi 1 ; Nagao, Noriko 1 ; Naito, Makoto 4 ; Kajimura, Shingo 5 ; Kimura, Hiroshi 6   VIAFID ORCID Logo  ; Osborne, Timothy F 7 ; Aburatani, Hiroyuki 8   VIAFID ORCID Logo  ; Kodama, Tatsuhiko 9 ; Inagaki, Takeshi 10 ; Sakai, Juro 11 

1  Division of Metabolic Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan 
2  Niigata College of Medical Technology, Niigata, Japan 
3  Rhelixa Inc., Tokyo, Japan; Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan 
4  Department of Pathology, Niigata Medical Center, Niigata, Japan 
5  Department of Cell and Tissue Biology, UCSF Diabetes Center, University of California, San Francisco, San Francisco, CA, USA 
6  Cell Biology Unit, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Japan 
7  Metabolic Disease Program, Sanford-Burnham Medical Research Institute, Orlando, FL, USA 
8  Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan 
9  Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan 
10  Division of Metabolic Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan; Laboratory of Epigenetics and Metabolism, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan 
11  Division of Metabolic Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan; Division of Molecular Physiology and Metabolism, Tohoku University Graduate School of Medicine, Sendai, Japan 
Pages
1-16
Publication year
2018
Publication date
Apr 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-03868-8
ProQuest document ID
2027569620
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.