Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 438191
Title Balancing of Histone H3K4 Methylation States by the Kdm5c/SMCX Histone Demethylase Modulates Promoter and Enhancer Function
Author(s) Outchkourov, N.S.; Muino Acuna, J.M.; Kaufmann, K.; IJken, W.F.J.; Groot Koerkamp, M.J.; Leenen, D. van; Graaf, P. de; Holstege, F.C.P.; Grosveld, F.; Timmers, H.T.M.
Source Cell Reports 3 (2013)4. - ISSN 2211-1247 - p. 1071 - 1079.
DOI http://dx.doi.org/10.1016/j.celrep.2013.02.030
Department(s) PRI BIOS Applied Metabolic Systems
PRI BIOS Applied Bioinformatics
Laboratory of Molecular Biology
Publication type Refereed Article in a scientific journal
Publication year 2013
Keyword(s) little-imaginal-discs - embryonic stem-cells - binding-protein 2 - gene-expression - distinct functions - self-renewal - human genome - transcription - differentiation - reveals
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
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