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PMID:10562550

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Citation

Nielsen, AL, Ortiz, JA, You, J, Oulad-Abdelghani, M, Khechumian, R, Gansmuller, A, Chambon, P and Losson, R (1999) Interaction with members of the heterochromatin protein 1 (HP1) family and histone deacetylation are differentially involved in transcriptional silencing by members of the TIF1 family. EMBO J. 18:6385-95

Abstract

Mammalian TIF1alpha and TIF1beta (KAP-1/KRIP-1) are related transcriptional intermediary factors that possess intrinsic silencing activity. TIF1alpha is believed to be a euchromatic target for liganded nuclear receptors, while TIF1beta may serve as a co-repressor for the large family of KRAB domain-containing zinc finger proteins. Here, we report an association of TIF1beta with both heterochromatin and euchromatin in interphase nuclei. Co-immunoprecipitation of nuclear extracts shows that endogenous TIF1beta, but not TIF1alpha, is associated with members of the heterochromatin protein 1 (HP1) family. However, in vitro, both TIF1alpha and TIF1beta interact with and phosphorylate the HP1 proteins. This interaction involves a conserved amino acid motif, which is critical for the silencing activity of TIF1beta but not TIF1alpha. We further show that trichostatin A, an inhibitor of histone deacetylases, can interfere with both TIF1 and HP1 silencing. The silencing activity of TIF1alpha appears to result chiefly from histone deacetylation, whereas that of TIF1beta may be mediated via both HP1 binding and histone deacetylation.

Links

PubMed PMC1171701 Online version:10.1093/emboj/18.22.6385

Keywords

Amino Acid Sequence; Animals; Cell Line; Cell Nucleus/metabolism; Chromatin/metabolism; Chromosomal Proteins, Non-Histone/isolation & purification; Chromosomal Proteins, Non-Histone/metabolism; Cloning, Molecular; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Enzyme Inhibitors/pharmacology; Euchromatin; Gene Expression Regulation; Heterochromatin/metabolism; Histone Deacetylase Inhibitors; Histone Deacetylases/metabolism; Histones/metabolism; Humans; Hydroxamic Acids/pharmacology; Mice; Molecular Sequence Data; Nuclear Proteins/chemistry; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Phosphorylation; Recombinant Fusion Proteins; Repressor Proteins/chemistry; Repressor Proteins/genetics; Repressor Proteins/metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Transcription Factors/chemistry; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription, Genetic; Transcriptional Activation; Zinc Fingers

Significance

Annotations

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

MOUSE:CBX3

located_in

GO:0000792: heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CBX3

acts_upstream_of_or_within

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CBX1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q62318
PR:Q64127

F

Seeded From UniProt

complete

MOUSE:CBX1

acts_upstream_of_or_within

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CBX5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q62318
PR:Q64127

F

Seeded From UniProt

complete

MOUSE:CBX5

acts_upstream_of_or_within

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TIF1B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P83917

F

Seeded From UniProt

complete

MOUSE:TIF1B

located_in

GO:0005654: nucleoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TIF1B

located_in

GO:0000791: euchromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TIF1B

located_in

GO:0000792: heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TIF1B

acts_upstream_of_or_within

GO:0006468: protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TIF1B

enables

GO:0004672: protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TIF1B

NOT|located_in

GO:0005730: nucleolus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TIF1B

acts_upstream_of_or_within

GO:0046777: protein autophosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TIF1B

acts_upstream_of_or_within

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TIF1A

acts_upstream_of_or_within

GO:0006468: protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TIF1A

enables

GO:0004672: protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TIF1A

acts_upstream_of_or_within

GO:0046777: protein autophosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TIF1A

acts_upstream_of_or_within

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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