@article{06b5addc20d24602a13f00d252e53ad7,
title = "Balancing of Histone H3K4 Methylation States by the Kdm5c/SMCX Histone Demethylase Modulates Promoter and Enhancer Function",
abstract = "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.",
author = "Outchkourov, {Nikolay S.} and Mui{\~n}o, {Jose M.} and Kerstin Kaufmann and {Van IJcken}, {Wilfred F.J.} and Koerkamp, {Marian J.Groot} and {Van Leenen}, Dik and {De Graaf}, Petra and Holstege, {Frank C.P.} and Grosveld, {Frank G.} and Timmers, {H. T.Marc}",
note = "Funding Information: We are grateful to Pascal Jansen and Dr. Michiel Vermeulen for mass spectrometry, and Hetty van Teeffelen for technical assistance. We thank Dr. Kaoru Tominaga and Dr. Olivia Pereira-Smith for the MRG15, Dr. Rene Bernards for the HA-c-MYC, Dr. Boudewijn Burgering for the Kdm5a, Dr. Yang Shi for the Kdm5b and Kdm5c, Dr. Andrew Sharrocks for the Flag-ELK1, and Dr. Sjaak Philipsen for the GATA expression vectors. We acknowledge Dr. Francis Stewart for reagents and protocols for BAC recombineering. We also thank Dr. Pim Pijnappel and the other members of the Timmers laboratory for advice and discussion, and Dr. Michiel Vermeulen for a critical reading of the manuscript. This work was funded by the European Union (EUTRACC LSHG-CT-2006-037445), The Netherlands Proteomics Centre, and NWO-CWO (TOP#700.57.302). ",
year = "2013",
month = apr,
day = "25",
doi = "10.1016/j.celrep.2013.02.030",
language = "English",
volume = "3",
pages = "1071--1079",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}