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PMID:19578370

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Citation

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

Abstract

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.

Links

PubMed Online version:10.1038/ncb1914

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TTF1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q91YE5

F

Seeded From UniProt

complete

MOUSE:BAZ2A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q923E4

F

Seeded From UniProt

complete

MOUSE:BAZ2A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q62187

F

Seeded From UniProt

complete

MOUSE:BAZ2A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9D1P2

F

Seeded From UniProt

complete

MOUSE:BAZ2A

involved_in

GO:0000183: rDNA heterochromatin assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BAZ2A

located_in

GO:0033553: rDNA heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BAZ2A

located_in

GO:0005730: nucleolus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:KAT8

enables

GO:0016407: acetyltransferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:KAT8

enables

GO:0019899: enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q91YE5

F

Seeded From UniProt

complete

MOUSE:SIRT1

enables

GO:0033558: protein deacetylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:SIRT1

enables

GO:0019899: enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q91YE5

F

Seeded From UniProt

complete

MOUSE:BAZ2A

involved_in

GO:0000183: chromatin silencing at rDNA

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BAZ2A

enables

GO:0070577: lysine-acetylated histone binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:BAZ2A

part_of

GO:0033553: rDNA heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BAZ2A

involved_in

GO:0006306: DNA methylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BAZ2A

part_of

GO:0005730: nucleolus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BAZ2A

part_of

GO:0005677: chromatin silencing complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BAZ2A

enables

GO:0003723: RNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:SIR1

enables

GO:0019899: enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q91YE5

F

Seeded From UniProt

complete

MOUSE:SIR1

enables

GO:0033558: protein deacetylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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