Protein kinase Msk1 physically and functionally interacts with the KMT2A/MLL1 methyltransferase complex and contributes to the regulation of multiple target genes

dc.contributor.authorWiersma, Maaike
dc.contributor.authorBussiere, Marianne
dc.contributor.authorHalsall, John A.
dc.contributor.authorTuran, Nil
dc.contributor.authorSlany, Robert
dc.contributor.authorTurner, Bryan M.
dc.contributor.authorNightingale, Karl P.
dc.date.accessioned2017-01-10
dc.date.available2017-01-04
dc.date.created2016
dc.date.issued2017-01-10
dc.description.abstractBackground The KMT2A/MLL1 lysine methyltransferase complex is an epigenetic regulator of selected developmental genes, in part through the SET domain-catalysed methylation of H3K4. It is essential for normal embryonic development and haematopoiesis and frequently mutated in cancer. The catalytic properties and targeting of KMT2A/MLL1 depend on the proteins with which it complexes and the post-translational protein modifications which some of these proteins put in place, though detailed mechanisms remain unclear. Results KMT2A/MLL1 (both native and FLAG-tagged) and Msk1 (RPS6KA5) co-immunoprecipitated in various cell types. KMT2A/MLL1 and Msk1 knockdown demonstrated that the great majority of genes whose activity changed on KTM2A/MLL1 knockdown, responded comparably to Msk1 knockdown, as did levels of H3K4 methylation and H3S10 phosphorylation at KTM2A target genes HoxA4, HoxA5. Knockdown experiments also showed that KMT2A/MLL1 is required for the genomic targeting of Msk1, but not vice versa. Conclusion The KMT2A/MLL1 complex is associated with, and functionally dependent upon, the kinase Msk1, part of the MAP kinase signalling pathway. We propose that Msk1-catalysed phosphorylation at H3 serines 10 and 28, supports H3K4 methylation by the KMT2A/MLL1 complex both by making H3 a more attractive substrate for its SET domain, and improving target gene accessibility by prevention of HP1- and Polycomb-mediated chromatin condensation.en
dc.identifier.citationEpigenetics & Chromatin 9 (2016). <http://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-016-0103-3>
dc.identifier.doihttps://doi.org/10.1186/s13072-016-0103-3
dc.identifier.opus-id8064
dc.identifier.urihttps://open.fau.de/handle/openfau/8064
dc.identifier.urnurn:nbn:de:bvb:29-opus4-80643
dc.language.isoen
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/de/deed.de
dc.subjectMLL1 complex
dc.subjectChromatin
dc.subjectHistone modification
dc.subjectSignal transduction
dc.subjectGene regulation
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titleProtein kinase Msk1 physically and functionally interacts with the KMT2A/MLL1 methyltransferase complex and contributes to the regulation of multiple target genesen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.journal.titleEpigenetics & Chromatin
local.journal.volume9
local.sendToDnbfree*
local.subject.fakultaetNaturwissenschaftliche Fakultät
local.subject.gnd-
local.subject.sammlungUniversität Erlangen-Nürnberg / Open Access Artikel ohne Förderung / Open Access Artikel ohne Förderung 2016
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