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

• DOI: 10.1016/j.celrep.2013.02.030
• Publication Date: 2013-03-28T15:34:24Z
• Authors: Nikolay S. Outchk...; Jose M. Muiño; Kerstin Kaufmann; Wilfred F.J. van ...; Marian J. Groot K...; Dik van Leenen; Petra de Graaf; Frank C.P. Holstege; Frank G. Grosveld; H.T. Marc Timmers
• Keywords: H3K4me3; Demethylase; Histone Methylation

The functional organization of eukaryotic genomes correlates with specific patterns histone methylations. Regulatory regions in such as enhancers and promoters differ their extent methylation H3 at lysine-4 (H3K4), but it is largely unknown how the different states are specified controlled. Here, we show that Kdm5c/Jarid1c/SMCX member Kdm5 family H3K4 demethylases can be recruited to both enhancer promoter elements mouse embryonic stem cells neuronal progenitor cells. Knockdown Kdm5c deregulates transcription via local increases H3K4me3. Our data indicate by restricting H3K4me3 modification core promoters, dampens transcription, stimulates activity. Remarkably, an impaired function activates intrinsic activity Kdm5c-bound distal elements. results demonstrate demethylase plays a crucial dynamic role discrimination between promoters.