2. Academic Validation
  3. Pontin arginine methylation by CARM1 is crucial for epigenetic regulation of autophagy

Pontin arginine methylation by CARM1 is crucial for epigenetic regulation of autophagy

  • Nat Commun. 2020 Dec 8;11(1):6297. doi: 10.1038/s41467-020-20080-9.
Young Suk Yu 1,  Hijai R Shin 1 2,  Dongha Kim 3,  Seon Ah Baek 1,  Seon Ah Choi 1,  Hyejin Ahn 1,  Amen Shamim 4,  Jeonghwan Kim 5 6,  Ik Soo Kim 1,  Kyeong Kyu Kim 4,  Kyoung-Jae Won 5 6,  Sung Hee Baek 7
Affiliations

Affiliations

  • 1 Creative Research Initiatives Center for Epigenetic Code and Diseases, Department of Biological Sciences, Seoul National University, Seoul, 08826, South Korea.
  • 2 Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, 94720, USA.
  • 3 Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea.
  • 4 Department of Molecular Cell Biology, School of Medicine, Sungkyunkwan University, Suwon, 16419, South Korea.
  • 5 Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200, Copenhagen N, Denmark.
  • 6 Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen N, Denmark.
  • 7 Creative Research Initiatives Center for Epigenetic Code and Diseases, Department of Biological Sciences, Seoul National University, Seoul, 08826, South Korea. [email protected].
PMID: 33293536 DOI: 10.1038/s41467-020-20080-9
Abstract

Autophagy is a catabolic process through which cytoplasmic components are degraded and recycled in response to various stresses including starvation. Recently, transcriptional and epigenetic regulations of Autophagy have emerged as essential mechanisms for maintaining homeostasis. Here, we identify that coactivator-associated arginine methyltransferase 1 (CARM1) methylates Pontin chromatin-remodeling factor under glucose starvation, and methylated Pontin binds Forkhead Box O 3a (FOXO3a). Genome-wide analyses and biochemical studies reveal that methylated Pontin functions as a platform for recruiting Tip60 Histone Acetyltransferase with increased H4 acetylation and subsequent activation of Autophagy genes regulated by FOXO3a. Surprisingly, CARM1-Pontin-FOXO3a signaling axis can work in the distal regions and activate Autophagy genes through enhancer activation. Together, our findings provide a signaling axis of CARM1-Pontin-FOXO3a and further expand the role of CARM1 in nuclear regulation of Autophagy.

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