Genomics

Dataset Information

299

The Kdm5c histone demethylase controls enhancer and promoter function.


ABSTRACT: Here, we show that the Kdm5c/Smcx member of the Jarid1 family of H3K4 demethylases is recruited to both enhancer and core promoter elements in ES and neuronal progenitor cells (NPC). Knockdown of Kdm5c deregulates transcription via a local increase in H3K4me3. While at core promoters the function of Kdm5c is to restrict transcription, loss of Kdm5c impairs enhancer function. Remarkably, an impaired enhancer function activates promoter activity from Kdm5c-bound intergenic regions. Our results demonstrate that the Kdm5c demethylase plays a crucial role in the functional identity and discrimination of enhancers and core promoters. We speculate that this is related to recruitment of H3K4me3 binders like the TFIID and NURF complexes6-8. Providing functional identity to genomic regions through balancing enzymes that deposit and remove histone modifications may prove to be a general epigenetic mechanism for the functional indexing of eukaryotic genomes. Examination of the KDM5C binding sites in mouse embryonic stem cells and in neuronal progenitor cells. Effect of KDM5C knock down on H3K4me3 and H3K4me1 levels and gene expression.

ORGANISM(S): Mus musculus  

SUBMITTER: Richard van Schaik   H T Timmers  Nikolay S Outchkourov 

PROVIDER: E-GEOD-34975 | ArrayExpress | 2013-04-01

SECONDARY ACCESSION(S): GSE34975SRP010203PRJNA151105

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Balancing of histone H3K4 methylation states by the Kdm5c/SMCX histone demethylase modulates promoter and enhancer function.

Outchkourov Nikolay S NS   Muiño Jose M JM   Kaufmann Kerstin K   van Ijcken Wilfred F J WF   Groot Koerkamp Marian J MJ   van Leenen Dik D   de Graaf Petra P   Holstege Frank C P FC   Grosveld Frank G FG   Timmers H T Marc HT  

Cell reports 20130328 4


The functional organization of eukaryotic genomes correlates with specific patterns of histone methylations. Regulatory regions in genomes such as enhancers and promoters differ in their extent of methylation of histone H3 at lysine-4 (H3K4), but it is largely unknown how the different methylation states are specified and controlled. Here, we show that the Kdm5c/Jarid1c/SMCX member of the Kdm5 family of H3K4 demethylases can be recruited to both enhancer and promoter elements in mouse embryonic  ...[more]

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