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

Young Suk Yu, Hijai R. Shin, Dongha Kim, Seon Ah Baek, Seon Ah Choi, Hyejin Ahn, Amen Shamim, Jeonghwan Kim, Ik Soo Kim, Kyeong Kyu Kim, Kyoung-Jae Won and Sung Hee Baek ()
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Young Suk Yu: Seoul National University
Hijai R. Shin: Seoul National University
Dongha Kim: The Catholic University of Korea
Seon Ah Baek: Seoul National University
Seon Ah Choi: Seoul National University
Hyejin Ahn: Seoul National University
Amen Shamim: Sungkyunkwan University
Jeonghwan Kim: University of Copenhagen
Ik Soo Kim: Seoul National University
Kyeong Kyu Kim: Sungkyunkwan University
Kyoung-Jae Won: University of Copenhagen
Sung Hee Baek: Seoul National University

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-20080-9

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