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Zhou, Y, Schmitz, KM, Mayer, C, Yuan, X, Akhtar, A and Grummt, I (2009) Reversible acetylation of the chromatin remodelling complex NoRC is required for non-coding RNA-dependent silencing. Nat. Cell Biol. 11:1010-6

The SNF2h (sucrose non-fermenting protein 2 homologue)-containing chromatin-remodelling complex NoRC silences a fraction of ribosomal RNA genes (rDNA) by establishing a heterochromatic structure at the rDNA promoter. Here we show that the acetyltransferase MOF (males absent on the first) acetylates TIP5, the largest subunit of NoRC, at a single lysine residue, K633, adjacent to the TIP5 RNA-binding domain, and that the NAD(+)-dependent deacetylase SIRT1 (sirtuin-1) removes the acetyl group from K633. Acetylation regulates the interaction of NoRC with promoter-associated RNA (pRNA), which in turn affects heterochromatin formation, nucleosome positioning and rDNA silencing. Significantly, NoRC acetylation is responsive to the intracellular energy status and fluctuates during S phase. Activation of SIRT1 on glucose deprivation leads to deacetylation of K633, enhanced pRNA binding and an increase in heterochromatic histone marks. These results suggest a mechanism that links the epigenetic state of rDNA to cell metabolism and reveal another layer of epigenetic control that involves post-translational modification of a chromatin remodelling complex.

PubMed Online version:10.1038/ncb1914

Acetylation; Adenosine Triphosphatases/genetics; Adenosine Triphosphatases/metabolism; Animals; Blotting, Western; Cell Line; Cell Line, Tumor; Chromatin Assembly and Disassembly; Chromatin Immunoprecipitation; Chromosomal Proteins, Non-Histone/genetics; Chromosomal Proteins, Non-Histone/metabolism; Flow Cytometry; HeLa Cells; Heterochromatin/genetics; Histone Acetyltransferases/genetics; Histone Acetyltransferases/metabolism; Humans; Lysine/metabolism; Mice; NIH 3T3 Cells; RNA Interference; RNA, Ribosomal/genetics; S Phase; Sirtuin 1; Sirtuins/genetics; Sirtuins/metabolism