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2014 ; 289
(42
): 28956-70
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Physical and functional interactions between the histone H3K4 demethylase KDM5A
and the nucleosome remodeling and deacetylase (NuRD) complex
#MMPMID25190814
Nishibuchi G
; Shibata Y
; Hayakawa T
; Hayakawa N
; Ohtani Y
; Sinmyozu K
; Tagami H
; Nakayama J
J Biol Chem
2014[Oct]; 289
(42
): 28956-70
PMID25190814
show ga
Histone H3K4 methylation has been linked to transcriptional activation. KDM5A
(also known as RBP2 or JARID1A), a member of the KDM5 protein family, is an H3K4
demethylase, previously implicated in the regulation of transcription and
differentiation. Here, we show that KDM5A is physically and functionally
associated with two histone deacetylase complexes. Immunoaffinity purification of
KDM5A confirmed a previously described association with the SIN3B-containing
histone deacetylase complex and revealed an association with the nucleosome
remodeling and deacetylase (NuRD) complex. Sucrose density gradient and
sequential immunoprecipitation analyses further confirmed the stable association
of KDM5A with these two histone deacetylase complexes. KDM5A depletion led to
changes in the expression of hundreds of genes, two-thirds of which were also
controlled by CHD4, the NuRD catalytic subunit. Gene ontology analysis confirmed
that the genes commonly regulated by both KDM5A and CHD4 were categorized as
developmentally regulated genes. ChIP analyses suggested that CHD4 modulates H3K4
methylation levels at the promoter and coding regions of target genes. We further
demonstrated that the Caenorhabditis elegans homologues of KDM5 and CHD4 function
in the same pathway during vulva development. These results suggest that KDM5A
and the NuRD complex cooperatively function to control developmentally regulated
genes.
|*Gene Expression Regulation
[MESH]
|Animals
[MESH]
|Autoantigens/metabolism
[MESH]
|Caenorhabditis elegans/metabolism
[MESH]
|Cell Line, Tumor
[MESH]
|Chromatin/metabolism
[MESH]
|Gene Expression Profiling
[MESH]
|HeLa Cells
[MESH]
|Histones/metabolism
[MESH]
|Humans
[MESH]
|MCF-7 Cells
[MESH]
|Methylation
[MESH]
|Mi-2 Nucleosome Remodeling and Deacetylase Complex/*metabolism
[MESH]
|Nucleosomes/metabolism
[MESH]
|Protein Binding
[MESH]
|RNA, Small Interfering/metabolism
[MESH]
|Repressor Proteins/metabolism
[MESH]
|Retinoblastoma-Binding Protein 2/*metabolism
[MESH]