{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KMT2B is a Trithorax‐group histone methyltransferase that catalyzes the methylation of histone H3 lysine 4—a mark closely linked with transcriptional activation. In the context of gene regulation, KMT2B functions as an integral component of COMPASS‐like complexes that couple “reading” and “writing” of active chromatin marks. This methyltransferase activity is critical for establishing and maintaining H3K4 trimethylation at promoters and for implementing mono‐ and di‐methylation at enhancers, thereby “priming” key developmental genes for activation during differentiation.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genomic studies have underscored the pivotal role of KMT2B in human development and disease. For instance, loss‐of-function mutations in this gene have been identified as major causative events in congenital syndromes such as Kabuki syndrome, where aberrant chromatin modification leads to dysregulation of gene expression and developmental defects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, KMT2B operates in concert with core subunits such as WDR5 and menin to promote H3K4 methylation, a modification that is essential for proper HOX gene activation and the fine‐tuning of transcription during embryonic stem cell differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, studies in model systems have demonstrated that in pluripotent and differentiating cells KMT2B is required to maintain the “bivalent” chromatin state at promoters of developmental regulators. This poised configuration—characterized by the simultaneous presence of activating (H3K4me3) and repressive (H3K27me3) marks—ensures the timely activation of gene expression programs during cell fate transitions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Inactivation or mutation of KMT2B perturbs these epigenetic landscapes, leading not only to developmental anomalies but also to oncogenic transformation in various cancers, where dysregulated transcriptional programs contribute to tumorigenesis.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings establish KMT2B as a critical epigenetic regulator that integrates chromatin modification with transcriptional control. By orchestrating the deposition of H3K4 methyl marks at promoters and enhancers, KMT2B plays a dual role in both developmental gene regulation and in safeguarding against the aberrant gene expression patterns that underlie human diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sarah B Ng, Abigail W Bigham, Kati J Buckingham, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.646"}], "href": "https://doi.org/10.1038/ng.646"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20711175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20711175"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Joanna Wysocka, Tomek Swigut, Thomas A Milne, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2005.03.036"}], "href": "https://doi.org/10.1016/j.cell.2005.03.036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15960974"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15960974"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sergei Denissov, Helmut Hofemeister, Hendrik Marks, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mll2 is required for H3K4 trimethylation on bivalent promoters in embryonic stem cells, whereas Mll1 is redundant."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.102681"}], "href": "https://doi.org/10.1242/dev.102681"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24423662"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24423662"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Pengfei Wang, Chengqi Lin, Edwin R Smith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00924-09"}], "href": "https://doi.org/10.1128/MCB.00924-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19703992"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19703992"}]}]}]}