Arginine methylation of CRTC2 is critical in the transcriptional control of hepatic glucose metabolism

Hye Sook Han, Chang Yun Jung, Young Sil Yoon, Seri Choi, Dahee Choi, Geon Kang, Keun Gyu Park, Seong Tae Kim, Seung-Hoi Koo

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Fasting glucose homeostasis is maintained in part through cAMP (adenosine 3',5'-monophosphate)- dependent transcriptional control of hepatic gluconeogenesis by the transcription factor CREB (cAMP response element-binding protein) and its coactivator CRTC2 (CREB-regulated transcriptional coactivator 2). We showed that PRMT6 (protein arginine methyltransferase 6) promotes fasting-induced transcriptional activation of the gluconeogenic program involving CRTC2. Mass spectrometric analysis indicated that PRMT6 associated with CRTC2. In cells, PRMT6 mediated asymmetric dimethylation of multiple arginine residues of CRTC2, which enhanced the association of CRTC2 with CREB on the promoters of gluconeogenic enzyme-encoding genes. In mice, ectopic expression of PRMT6 promoted higher blood glucose concentrations, which were associated with increased expression of genes encoding gluconeogenic factors, whereas knockdown of hepatic PRMT6 decreased fasting glycemia and improved pyruvate tolerance. The abundance of hepatic PRMT6 was increased in mouse models of obesity and insulin resistance, and adenovirus-mediated depletion of PRMT6 restored euglycemia in these mice. We propose that PRMT6 is involved in the regulation of hepatic glucose metabolism in a CRTC2-dependent manner.

Original languageEnglish
JournalScience Signaling
Volume7
Issue number314
DOIs
Publication statusPublished - 2014 Feb 25

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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