| First Author | Takahashi H | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 5715 |
| PubMed ID | 36175407 | Mgi Jnum | J:336728 |
| Mgi Id | MGI:7344976 | Doi | 10.1038/s41467-022-33363-0 |
| Citation | Takahashi H, et al. (2022) MYPT1-PP1beta phosphatase negatively regulates both chromatin landscape and co-activator recruitment for beige adipogenesis. Nat Commun 13(1):5715 |
| abstractText | Protein kinase A promotes beige adipogenesis downstream from beta-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 1beta (MYPT1-PP1beta) phosphatase activity is inhibited via PKA-dependent phosphorylation, which increases phosphorylated JMJD1A and beige adipogenesis. Mechanistically, MYPT1-PP1beta depletion results in JMJD1A-mediated H3K9 demethylation and activation of the Ucp1 enhancer/promoter regions. Interestingly, MYPT1-PP1beta 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. |
