Page 14 - ebook

[A. Biochemistry/Molecular Biology] A-7

Pontin arginine methylation by CARM1 is crucial for

epigenetic regulation of autophagy

Dongha Kim¹*, Bok-im Cho¹

¹Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea

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.