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PMID:16236793

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Citation

McKinsey, TA, Kuwahara, K, Bezprozvannaya, S and Olson, EN (2006) Class II histone deacetylases confer signal responsiveness to the ankyrin-repeat proteins ANKRA2 and RFXANK. Mol. Biol. Cell 17:438-47

Abstract

Class II histone deacetylases (HDACs) contain unique amino-terminal extensions that mediate interactions with members of the myocyte enhancer factor-2 (MEF2) family of transcription factors and responsiveness to kinases, including Ca2+/calmodulin-dependent kinase (CaMK). Despite intense investigation of class II HDACs, little is known of MEF2-independent mechanisms for transcriptional repression by these chromatin-modifying enzymes. Here, we demonstrate that class II HDACs 4 and 5 physically associate with ankyrin-repeat proteins ANKRA2 and RFXANK (RFX-B/Tvl-1/ANKRA1). ANKRA2 is a megalin- and BKCa potassium channel-interacting factor, whereas RFXANK is a positive regulator of major histocompatibility complex II (MHC II) gene expression. HDAC4 and HDAC5 interact with the ankyrin repeats of ANKRA2 and RFXANK and, through association with RFXANK, repress MHC II promoter activation. HDACs 4 and 5 also repress endogenous HLA-DRA gene expression induced by CIITA. Phosphorylation of class II HDACs by CaMK results in CRM1-dependent nuclear export of HDAC/RFXANK complexes. These results define a novel transcriptional pathway under the control of class II HDACs and suggest a role for these transcriptional repressors as signal-responsive regulators of antigen presentation.

Links

PubMed PMC1345680 Online version:10.1091/mbc.E05-07-0612

Keywords

Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Animals; Ankyrins/genetics; Ankyrins/metabolism; Cell Line; Cercopithecus aethiops; Gene Expression Regulation; Histone Deacetylases/classification; Histone Deacetylases/genetics; Histone Deacetylases/metabolism; Macrophages/metabolism; Membrane Glycoproteins/genetics; Membrane Glycoproteins/metabolism; Mice; Promoter Regions, Genetic/genetics; Protein Binding; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Signal Transduction

Significance

Annotations

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

HUMAN:HDAC4

acts_upstream_of_or_within

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:XPO1

acts_upstream_of_or_within

GO:0006611: protein export from nucleus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ANRA2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UQL6

F

Seeded From UniProt

complete

MOUSE:ANRA2

located_in

GO:0005634: nucleus

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9UQL6

C

Seeded From UniProt

complete

MOUSE:ANRA2

located_in

GO:0005737: cytoplasm

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1098535
UniProtKB:Q9UQL6

C

Seeded From UniProt

complete

MOUSE:ANRA2

enables

GO:0042826: histone deacetylase binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HDAC5

acts_upstream_of_or_within

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RFXK

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UQL6

F

Seeded From UniProt

complete

MOUSE:RFXK

located_in

GO:0005634: nucleus

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9UQL6

C

Seeded From UniProt

complete

MOUSE:RFXK

enables

GO:0042826: histone deacetylase binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:RFXK

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HDAC5

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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