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To date, there is no effective therapy for DIPG. Transcriptomic analyses have revealed DIPGs have a distinct profile from other pediatric high-grade gliomas occurring in the cerebral hemispheres. These unique genomic characteristics coupled with the younger median age group suggest that DIPG has a developmental origin. The most frequent mutation in DIPG is a lysine to methionine (K27M) mutation that occurs on H3F3A and HIST1H3B\/C, genes encoding histone variants. The K27M mutation disrupts methylation by polycomb repressive complex 2 on histone H3 at lysine 27, leading to global hypomethylation. Histone 3 lysine 27 trimethylation is an important developmental regulator controlling gene expression. This review discusses the developmental and epigenetic mechanisms driving disease progression in DIPG, as well as the profound therapeutic implications of epigenetic programming.<\/jats:p>","DOI":"10.1093\/neuonc\/noz218","type":"journal-article","created":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T15:14:43Z","timestamp":1573226083000},"page":"195-206","source":"Crossref","is-referenced-by-count":25,"title":["Epigenetic reprogramming and chromatin accessibility in pediatric diffuse intrinsic pontine gliomas: a neural developmental disease"],"prefix":"10.1093","volume":"22","author":[{"given":"Flor M","family":"Mendez","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology and Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe J","family":"N\u00fa\u00f1ez","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology and Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria B","family":"Garcia-Fabiani","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology and Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Haase","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology and Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Carney","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology and Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica C","family":"Gauss","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology and Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oren J","family":"Becher","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Northwestern University, Chicago, Illinois"},{"name":"Ann & Robert Lurie Children\u2019s Hospital of Chicago, Division of Hematology-Oncology and Stem Cell Transplant, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro R","family":"Lowenstein","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology and Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria G","family":"Castro","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology 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