| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2039968 | Cell Reports | 2016 | 14 Pages |
•K779 of PGC-1α is methylated by SET7/9 and demethylated by LSD1•PGC-1α[K779me] recruits SAGA and Mediator at enhancers of target genes•PGC-1α[K779me] corresponds with NSUN7 and m5C eRNAs at PGC1α-regulated loci•Enrichment of m5C within eRNA coincides with fasting in vivo
SummaryThe Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) is a transcriptional co-activator that plays a central role in adapted metabolic responses. PGC-1α is dynamically methylated and unmethylated at the residue K779 by the methyltransferase SET7/9 and the Lysine Specific Demethylase 1A (LSD1), respectively. Interactions of methylated PGC-1α[K779me] with the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex, the Mediator members MED1 and MED17, and the NOP2/Sun RNA methytransferase 7 (NSUN7) reinforce transcription, and are concomitant with the m5C mark on enhancer RNAs (eRNAs). Consistently, loss of Set7/9 and NSun7 in liver cell model systems resulted in depletion of the PGC-1α target genes Pfkl, Sirt5, Idh3b, and Hmox2, which was accompanied by a decrease in the eRNAs levels associated with these loci. Enrichment of m5C within eRNA species coincides with metabolic stress of fasting in vivo. Collectively, these findings illustrate the complex epigenetic circuitry imposed by PGC-1α at the eRNA level to fine-tune energy metabolism.
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