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PMID:12198165

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Citation

Zhou, Y, Santoro, R and Grummt, I (2002) The chromatin remodeling complex NoRC targets HDAC1 to the ribosomal gene promoter and represses RNA polymerase I transcription. EMBO J. 21:4632-40

Abstract

Mammalian chromatin remodeling complexes are involved in both activation and repression of transcription. Here, we show that NoRC, a SNF2h- containing nucleolar chromatin remodeling complex, represses ribosomal gene transcription. NoRC-mediated rDNA silencing was alleviated by trichostatin A, indicating that histone deacetylation is causally involved in silencing. Chromatin immunoprecipitation experiments demonstrate that overexpression of TIP5, the large subunit of NoRC, mediates deacetylation of nucleosomes in the vicinity of the rDNA promoter. Protein-protein interaction assays reveal association of TIP5 with the histone deacetylase HDAC1 in vivo and in vitro. Deletion of the C-terminal PHD finger and bromodomain abolishes the interaction of TIP5 and HDAC1, and abrogates transcriptional repression. The results suggest that NoRC silences the rDNA locus by targeting the SIN3 corepressor complex to the rDNA promoter, thereby establishing a repressed chromatin structure.

Links

PubMed PMC126197

Keywords

3T3 Cells; Acetylation; Amino Acid Motifs; Animals; Cell Line; Chromatin/metabolism; Chromosomal Proteins, Non-Histone/chemistry; Chromosomal Proteins, Non-Histone/physiology; DNA, Ribosomal/genetics; Gene Silencing; Genes, rRNA; Histone Deacetylase 1; Histone Deacetylases/metabolism; Histones/metabolism; Macromolecular Substances; Mice; Multienzyme Complexes/metabolism; Nucleosomes/metabolism; Promoter Regions, Genetic; Protein Interaction Mapping; Protein Processing, Post-Translational; Protein Structure, Tertiary; RNA Polymerase I/antagonists & inhibitors; Recombinant Fusion Proteins/physiology; Sin3 Histone Deacetylase and Corepressor Complex; Trans-Activators/physiology; Transcription, Genetic

Significance

Annotations

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

MOUSE:HDAC1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q91YE5

F

Seeded From UniProt

complete

MOUSE:SIN3A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q91YE5

F

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

involved_in

GO:0000183: rDNA heterochromatin assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BAZ2A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q60520

F

Seeded From UniProt

complete

MOUSE:BAZ2A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O09106

F

Seeded From UniProt

complete

MOUSE:BAZ2A

involved_in

GO:0031065: positive regulation of histone deacetylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SMCA5

involved_in

GO:0031065: positive regulation of histone deacetylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SMCA5

involved_in

GO:0000183: rDNA heterochromatin assembly

ECO:0000314: direct assay evidence used in manual assertion

P

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:0016575: histone deacetylation

ECO:0000314: direct assay evidence used in manual assertion

P

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


See also

References

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