Hu, DeqingGao, XinCao, KaixiangMorgan, Marc Alard J.Mas Martín, GlòriaSmith, Edwin R.Volk, Andrew G.Bartom, Elizabeth T.Crispino, John D.Di Croce, LucianoShilatifard, Ali2018-06-192018-06-192017Hu 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.2017.01.0131097-2765http://hdl.handle.net/10230/34927The 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.application/pdfeng© 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-licenseinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.molcel.2017.01.013Cxxc domainHistone-lysine n-methyltransferaseKmt2bMll2ChromatinEmbryonic developmentGene expression regulationHistoneMouse embryonic stem cellPrimordial germ cellinfo:eu-repo/semantics/openAccess