RRC ID 73350
Author Takahashi H, Yang G, Yoneshiro T, Abe Y, Ito R, Yang C, Nakazono J, Okamoto-Katsuyama M, Uchida A, Arai M, Jin H, Choi H, Tumenjargal M, Xie S, Zhang J, Sagae H, Zhao Y, Yamaguchi R, Nomura Y, Shimizu Y, Yamada K, Yasuda S, Kimura H, Tanaka T, Wada Y, Kodama T, Aburatani H, Zhu MS, Inagaki T, Osborne TF, Kawamura T, Ishihama Y, Matsumura Y, Sakai J.
Title MYPT1-PP1β phosphatase negatively regulates both chromatin landscape and co-activator recruitment for beige adipogenesis.
Journal Nat Commun
Abstract Protein kinase A promotes beige adipogenesis downstream from β-adrenergic receptor signaling by phosphorylating proteins, including histone H3 lysine 9 (H3K9) demethylase JMJD1A. To ensure homeostasis, this process needs to be reversible however, this step is not well understood. We show that myosin phosphatase target subunit 1- protein phosphatase 1β (MYPT1-PP1β) phosphatase activity is inhibited via PKA-dependent phosphorylation, which increases phosphorylated JMJD1A and beige adipogenesis. Mechanistically, MYPT1-PP1β depletion results in JMJD1A-mediated H3K9 demethylation and activation of the Ucp1 enhancer/promoter regions. Interestingly, MYPT1-PP1β also dephosphorylates myosin light chain which regulates actomyosin tension-mediated activation of YAP/TAZ which directly stimulates Ucp1 gene expression. Pre-adipocyte specific Mypt1 deficiency increases cold tolerance with higher Ucp1 levels in subcutaneous white adipose tissues compared to control mice, confirming this regulatory mechanism in vivo. Thus, we have uncovered regulatory cross-talk involved in beige adipogenesis that coordinates epigenetic regulation with direct activation of the mechano-sensitive YAP/TAZ transcriptional co-activators.
Volume 13(1)
Pages 5715
Published 2022-9-29
DOI 10.1038/s41467-022-33363-0
PII 10.1038/s41467-022-33363-0
PMID 36175407
PMC PMC9523048
MeSH Actomyosin Adipogenesis* / genetics Animals Chromatin* Cyclic AMP-Dependent Protein Kinases Epigenesis, Genetic Histones Lysine Mice Myosin Light Chains Myosin-Light-Chain Phosphatase / genetics Myosin-Light-Chain Phosphatase / metabolism* Phosphoric Monoester Hydrolases
IF 12.121
DNA material CSII-EF-MCS-IRES2-Venus (RDB04384) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394)