NAD+-SIRT1 control of H3K4 trimethylation through circadian deacetylation of MLL1

Lorena Aguilar-Arnal, Sayako Katada, Ricardo Orozco-Solis, Paolo Sassone-Corsi

研究成果: Contribution to journalArticle査読

67 被引用数 (Scopus)

抄録

The circadian clock controls the transcription of hundreds of genes through specific chromatin-remodeling events. The histone methyltransferase mixed-lineage leukemia 1 (MLL1) coordinates recruitment of CLOCK-BMAL1 activator complexes to chromatin, an event associated with cyclic trimethylation of histone H3 Lys4 (H3K4) at circadian promoters. Remarkably, in mouse liver circadian H3K4 trimethylation is modulated by SIRT1, an NAD+-dependent deacetylase involved in clock control. We show that mammalian MLL1 is acetylated at two conserved residues, K1130 and K1133. Notably, MLL1 acetylation is cyclic, controlled by the clock and by SIRT1, and it affects the methyltransferase activity of MLL1. Moreover, H3K4 methylation at clock-controlled-gene promoters is influenced by pharmacological or genetic inactivation of SIRT1. Finally, levels of MLL1 acetylation and H3K4 trimethylation at circadian gene promoters depend on NAD+ circadian levels. These findings reveal a previously unappreciated regulatory pathway between energy metabolism and histone methylation.

本文言語英語
ページ(範囲)312-318
ページ数7
ジャーナルNature Structural and Molecular Biology
22
4
DOI
出版ステータス出版済み - 4 7 2015

All Science Journal Classification (ASJC) codes

  • 構造生物学
  • 分子生物学

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