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PMID:21549307

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Citation

Rowbotham, SP, Barki, L, Neves-Costa, A, Santos, F, Dean, W, Hawkes, N, Choudhary, P, Will, WR, Webster, J, Oxley, D, Green, CM, Varga-Weisz, P and Mermoud, JE (2011) Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1. Mol. Cell 42:285-96

Abstract

Epigenetic marks such as posttranslational histone modifications specify the functional states of underlying DNA sequences, though how they are maintained after their disruption during DNA replication remains a critical question. We identify the mammalian SWI/SNF-like protein SMARCAD1 as a key factor required for the re-establishment of repressive chromatin. The ATPase activity of SMARCAD1 is necessary for global deacetylation of histones H3/H4. In this way, SMARCAD1 promotes methylation of H3K9, the establishment of heterochromatin, and faithful chromosome segregation. SMARCAD1 associates with transcriptional repressors including KAP1, histone deacetylases HDAC1/2 and the histone methyltransferase G9a/GLP and modulates the interaction of HDAC1 and KAP1 with heterochromatin. SMARCAD1 directly interacts with PCNA, a central component of the replication machinery, and is recruited to sites of DNA replication. Our findings suggest that chromatin remodeling by SMARCAD1 ensures that silenced loci, such as pericentric heterochromatin, are correctly perpetuated.

Links

PubMed Online version:10.1016/j.molcel.2011.02.036

Keywords

Acetylation; Adenosine Triphosphatases/metabolism; Animals; Blotting, Western; Cell Line; Cells, Cultured; Chromatin/genetics; Chromatin/metabolism; DNA Helicases/genetics; DNA Helicases/metabolism; DNA Replication; Gene Expression Regulation; HEK293 Cells; HeLa Cells; Heterochromatin/genetics; Heterochromatin/metabolism; Histone Deacetylase 1/metabolism; Histone-Lysine N-Methyltransferase/metabolism; Histones/metabolism; Humans; Methylation; Mice; NIH 3T3 Cells; Proliferating Cell Nuclear Antigen/metabolism; Protein Binding; RNA Interference; Reverse Transcriptase Polymerase Chain Reaction; S Phase

Significance

Annotations

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

HUMAN:PARP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H4L7

F

Seeded From UniProt

complete

HUMAN:PCNA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H4L7

F

Seeded From UniProt

complete

MOUSE:SMRCD

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SMRCD

located_in

GO:0000792: heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CBX3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H4L7

F

Seeded From UniProt

complete

HUMAN:TIF1B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H4L7

F

Seeded From UniProt

complete

HUMAN:HDAC1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H4L7

F

Seeded From UniProt

complete

HUMAN:HDAC2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H4L7

F

Seeded From UniProt

complete

HUMAN:EHMT2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H4L7

F

Seeded From UniProt

complete

HUMAN:SMRCD

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P12004

F

Seeded From UniProt

complete

HUMAN:SMRCD

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13263

F

Seeded From UniProt

complete

HUMAN:SMRCD

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13185

F

Seeded From UniProt

complete

HUMAN:SMRCD

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96KQ7

F

Seeded From UniProt

complete

HUMAN:SMRCD

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P09874

F

Seeded From UniProt

complete

HUMAN:SMRCD

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92769

F

Seeded From UniProt

complete

HUMAN:SMRCD

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13547

F

Seeded From UniProt

complete

HUMAN:SMRCD

located_in

GO:0043596: nuclear replication fork

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SMRCD

involved_in

GO:0006338: chromatin remodeling

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMRCD

part_of

GO:0043596: nuclear replication fork

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SMRCD

involved_in

GO:0051304: chromosome separation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMRCD

involved_in

GO:0070932: histone H3 deacetylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMRCD

involved_in

GO:0070933: histone H4 deacetylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.