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Title:	Not all H3K4 Methylations are created equal: Mll2/COMPASS dependency in primordial germ cell specification
Author:	Hu, Deqing; Gao, Xin; Cao, Kaixiang; Morgan, Marc Alard J.; Mas Martín, Glòria; Smith, Edwin R.; Volk, Andrew G.; Bartom, Elizabeth T.; Crispino, John D.; Di Croce, Luciano; Shilatifard, Ali
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.
Abstract:	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.
Subject(s):	-Cxxc domain -Histone-lysine n-methyltransferase -Kmt2b -Mll2 -Chromatin -Embryonic development -Gene expression regulation -Histone -Mouse embryonic stem cell -Primordial germ cell
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
Document type:	Article Article - Published version
Published by:	Elsevier
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