Balancing of Histone H3K4 Methylation States by the Kdm5c/SMCX Histone Demethylase Modulates Promoter and Enhancer Function

Nikolay S. Outchkourov, Jose M. Muiño, Kerstin Kaufmann, Wilfred F.J. Van IJcken, Marian J.Groot Koerkamp, Dik Van Leenen, Petra De Graaf, Frank C.P. Holstege, Frank G. Grosveld, H. T.Marc Timmers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

93 Citaten (Scopus)

Samenvatting

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 stem cells and in neuronal progenitor cells. Knockdown of Kdm5c deregulates transcription via local increases in H3K4me3. Our data indicate that by restricting H3K4me3 modification at core promoters, Kdm5c dampens transcription, but at enhancers Kdm5c stimulates their activity. Remarkably, an impaired enhancer function activates the intrinsic promoter activity of Kdm5c-bound distal elements. Our results demonstrate that the Kdm5c demethylase plays a crucial and dynamic role in the functional discrimination between enhancers and core promoters.

Originele taal-2Engels
Pagina's (van-tot)1071-1079
Aantal pagina's9
TijdschriftCell Reports
Volume3
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - 25 apr. 2013
Extern gepubliceerdJa

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