Histone arginine methyltransferase CARM1 Is Crucial for Epigenetic Regulation of Starvation-induced Autophagy

Autophagy is a highly conserved self-digestion process, essential to maintain homeostasis and viability in response to nutrient starvation. Although the components of autophagy in the cytoplasm have been well-studied, molecular basis for the epigenetic regulation of autophagy is poorly understood. Here, we identify histone arginine methyltransferase CARM1 as a critical component of autophagy. We found that nutrient starvation increased CARM1 protein level and subsequently histone H3R17 dimethylation. Genome-wide analyses reveal that CARM1 exerts transcriptional coactivator function on autophagy-related genes and lysosomal genes through TFEB. Our findings demonstrate a previously unrecognized role of CARM1-dependent histone arginine methylation as a critical nuclear event of autophagy. 1) Gene expression profiling of WT and Carm1 KO MEFs under nutrient rich condition or glucose starvation. 2) Examination of histone H3R17 dimethylation in WT MEFs upon glucose starvation