Not all H3K4 Methylations are created equal: Mll2/COMPASS dependency in primordial germ cell specification

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• dc.contributor.author Hu, Deqingca
• dc.contributor.author Gao, Xinca
• dc.contributor.author Cao, Kaixiangca
• dc.contributor.author Morgan, Marc Alard J.ca
• dc.contributor.author Mas Martín, Glòriaca
• dc.contributor.author Smith, Edwin R.ca
• dc.contributor.author Volk, Andrew G.ca
• dc.contributor.author Bartom, Elizabeth T.ca
• dc.contributor.author Crispino, John D.ca
• dc.contributor.author Di Croce, Lucianoca
• dc.contributor.author Shilatifard, Alica
• dc.date.accessioned 2018-06-19T07:53:55Z
• dc.date.available 2018-06-19T07:53:55Z
• dc.date.issued 2017
• dc.description.abstract The spatiotemporal regulation of gene expression is central for cell-lineage specification during embryonic development and is achieved through the combinatorial action of transcription factors/co-factors and epigenetic states at cis-regulatory elements. Here, we show that in addition to implementing H3K4me3 at promoters of bivalent genes, Mll2 (KMT2B)/COMPASS can also implement H3K4me3 at a subset of non-TSS regulatory elements, a subset of which shares epigenetic signatures of active enhancers. Our mechanistic studies reveal that association of Mll2's CXXC domain with CpG-rich regions plays an instrumental role for chromatin targeting and subsequent implementation of H3K4me3. Although Mll2/COMPASS is required for H3K4me3 implementation on thousands of loci, generation of catalytically mutant MLL2/COMPASS demonstrated that H3K4me3 implemented by this enzyme was essential for expression of a subset of genes, including those functioning in the control of transcriptional programs during embryonic development. Our findings suggest that not all H3K4 trimethylations implemented by MLL2/COMPASS are functionally equivalent.
• dc.description.sponsorship D.H. was supported by the Robert H. Lurie Comprehensive Cancer Center - Translational Bridge Program Fellowship in Lymphoma Research. G.M. received the support of Ia Convocatoria de Ayudas Fundación BBVA a Investigadores, Innovadores y Creadores Culturales. A.V. was supported by NIH training grant T32CA080621. These studies were further supported by grants from the Spanish “Ministerio de Educación y Ciencia” (SAF2013-48926-P) and AGAUR to L.D.C., and NIH grants R01CA101774 to J.D.C., R50CA211428 to E.R.S., and R35CA197569 to A.S.
• dc.format.mimetype application/pdf
• dc.identifier.citation Hu D, Gao X, Cao K, Morgan MA, Mas G, Smith ER et al. Not All H3K4 Methylations Are Created Equal: Mll2/COMPASS Dependency in Primordial Germ Cell Specification. Mol Cell. 2017 Feb 2;65(3):460-75. DOI: 10.1016/j.molcel.2017.01.013
• dc.identifier.doi http://dx.doi.org/10.1016/j.molcel.2017.01.013
• dc.identifier.issn 1097-2765
• dc.identifier.uri http://hdl.handle.net/10230/34927
• dc.language.iso eng
• dc.publisher Elsevierca
• dc.relation.ispartof Molecular Cell. 2017 Feb 2;65(3):460-75
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-48926-P
• dc.rights © Elsevier This is the published version of an article http://dx.doi.org/10.1016/j.molcel.2017.01.013 that appeared in the journal Molecular Cell. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: https://www.elsevier.com/about/our-business/policies/open-access-licenses/elsevier-user-license
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Cxxc domain
• dc.subject.keyword Histone-lysine n-methyltransferase
• dc.subject.keyword Kmt2b
• dc.subject.keyword Mll2
• dc.subject.keyword Chromatin
• dc.subject.keyword Embryonic development
• dc.subject.keyword Gene expression regulation
• dc.subject.keyword Histone
• dc.subject.keyword Mouse embryonic stem cell
• dc.subject.keyword Primordial germ cell
• dc.title Not all H3K4 Methylations are created equal: Mll2/COMPASS dependency in primordial germ cell specificationca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion