Reversible acetylation of the chromatin remodelling complex NoRC is required for non-coding RNA-dependent silencing.
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.
Zhou
Yonggang
Y
German Cancer Research Center, Division of Molecular Biology of the Cell II, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany.
Schmitz
Kerstin-Maike
KM
Mayer
Christine
C
Yuan
Xuejun
X
Akhtar
Asifa
A
Grummt
Ingrid
I
D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D006367:HeLa Cells; D006570:Heterochromatin / Q000235:genetics; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D034622:RNA Interference; D012335:RNA, Ribosomal / Q000235:genetics*; D016196:S Phase; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism; D000092468:Bromodomain Containing Proteins
D000251:Adenosine Triphosphatases; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D051548:Histone Acetyltransferases; D008239:Lysine; D012335:RNA, Ribosomal; D056564:Sirtuin 1; D037761:Sirtuins; C436708:BAZ2A protein, human; D000092468:Bromodomain Containing Proteins; C499051:Baz2a protein, mouse; C496552:KAT8 protein, human; C000622683:Kat8 protein, mouse; C447939:SIRT1 protein, human; C470545:Sirt1 protein, mouse; C409462:SMARCA5 protein, human