{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:22:26Z","timestamp":1791555746585,"version":"4.3.4"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T00:00:00Z","timestamp":1488153600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T00:00:00Z","timestamp":1488153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2017,4]]},"DOI":"10.1038\/nm.4296","type":"journal-article","created":{"date-parts":[[2017,3,4]],"date-time":"2017-03-04T00:21:46Z","timestamp":1488586906000},"page":"493-500","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":428,"title":["Therapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas"],"prefix":"10.1038","volume":"23","author":[{"given":"Andrea","family":"Piunti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rintaro","family":"Hashizume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth T","family":"Bartom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig M","family":"Horbinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy A","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J","family":"Rendleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanhong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoh-hei","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley R","family":"Woodfin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2879-3789","authenticated-orcid":false,"given":"Alexander V","family":"Misharin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nebiyu A","family":"Abshiru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishi R","family":"Lulla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M","family":"Saratsis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8815-3372","authenticated-orcid":false,"given":"Neil L","family":"Kelleher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C David","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Shilatifard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,27]]},"reference":[{"key":"BFnm4296_CR1","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/pr.2013.194","volume":"75","author":"KM Schroeder","year":"2014","unstructured":"Schroeder, K.M., Hoeman, C.M. & Becher, O.J. Children are not just little adults: recent advances in understanding of diffuse intrinsic pontine glioma biology. Pediatr. Res. 75, 205\u2013209 (2014).","journal-title":"Pediatr. Res."},{"key":"BFnm4296_CR2","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/nature10833","volume":"482","author":"J Schwartzentruber","year":"2012","unstructured":"Schwartzentruber, J. et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482, 226\u2013231 (2012).","journal-title":"Nature"},{"key":"BFnm4296_CR3","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/ng.1102","volume":"44","author":"G Wu","year":"2012","unstructured":"Wu, G. et al. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat. Genet. 44, 251\u2013253 (2012).","journal-title":"Nat. Genet."},{"key":"BFnm4296_CR4","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1126\/science.1232245","volume":"340","author":"PW Lewis","year":"2013","unstructured":"Lewis, P.W. et al. Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science 340, 857\u2013861 (2013).","journal-title":"Science"},{"key":"BFnm4296_CR5","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1126\/science.1255104","volume":"345","author":"HM Herz","year":"2014","unstructured":"Herz, H.M. et al. Histone H3 lysine-to-methionine mutants as a paradigm to study chromatin signaling. Science 345, 1065\u20131070 (2014).","journal-title":"Science"},{"key":"BFnm4296_CR6","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1016\/j.ccr.2013.10.006","volume":"24","author":"S Bender","year":"2013","unstructured":"Bender, S. et al. Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell 24, 660\u2013672 (2013).","journal-title":"Cancer Cell"},{"key":"BFnm4296_CR7","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1101\/gad.217778.113","volume":"27","author":"KM Chan","year":"2013","unstructured":"Chan, K.M. et al. The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression. Genes Dev. 27, 985\u2013990 (2013).","journal-title":"Genes Dev."},{"key":"BFnm4296_CR8","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1038\/nm.3716","volume":"20","author":"R Hashizume","year":"2014","unstructured":"Hashizume, R. et al. Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nat. Med. 20, 1394\u20131396 (2014).","journal-title":"Nat. Med."},{"key":"BFnm4296_CR9","doi-asserted-by":"publisher","first-page":"4453","DOI":"10.1073\/pnas.1101657108","volume":"108","author":"M Monje","year":"2011","unstructured":"Monje, M. et al. Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma. Proc. Natl. Acad. Sci. USA 108, 4453\u20134458 (2011).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm4296_CR10","doi-asserted-by":"publisher","first-page":"11316","DOI":"10.1038\/ncomms11316","volume":"7","author":"N Justin","year":"2016","unstructured":"Justin, N. et al. Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2. Nat. Commun. 7, 11316 (2016).","journal-title":"Nat. Commun."},{"key":"BFnm4296_CR11","doi-asserted-by":"publisher","first-page":"aad9780","DOI":"10.1126\/science.aad9780","volume":"352","author":"A Piunti","year":"2016","unstructured":"Piunti, A. & Shilatifard, A. Epigenetic balance of gene expression by Polycomb and COMPASS families. Science 352, aad9780 (2016).","journal-title":"Science"},{"key":"BFnm4296_CR12","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1101\/gad.415507","volume":"21","author":"AP Bracken","year":"2007","unstructured":"Bracken, A.P. et al. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev. 21, 525\u2013530 (2007).","journal-title":"Genes Dev."},{"key":"BFnm4296_CR13","doi-asserted-by":"publisher","first-page":"3649","DOI":"10.1038\/ncomms4649","volume":"5","author":"A Piunti","year":"2014","unstructured":"Piunti, A. et al. Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication. Nat. Commun. 5, 3649 (2014).","journal-title":"Nat. Commun."},{"key":"BFnm4296_CR14","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1016\/j.cell.2013.09.053","volume":"155","author":"D Hnisz","year":"2013","unstructured":"Hnisz, D. et al. Super-enhancers in the control of cell identity and disease. Cell 155, 934\u2013947 (2013).","journal-title":"Cell"},{"key":"BFnm4296_CR15","doi-asserted-by":"publisher","first-page":"a018663","DOI":"10.1101\/cshperspect.a018663","volume":"6","author":"J Qi","year":"2014","unstructured":"Qi, J. Bromodomain and extraterminal domain inhibitors (BETi) for cancer therapy: chemical modulation of chromatin structure. Cold Spring Harb. Perspect. Biol. 6, a018663 (2014).","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"BFnm4296_CR16","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/nrm3953","volume":"16","author":"I Jonkers","year":"2015","unstructured":"Jonkers, I. & Lis, J.T. Getting up to speed with transcription elongation by RNA polymerase II. Nat. Rev. Mol. Cell Biol. 16, 167\u2013177 (2015).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"BFnm4296_CR17","doi-asserted-by":"publisher","first-page":"5208","DOI":"10.1038\/sj.onc.1206558","volume":"22","author":"U Galderisi","year":"2003","unstructured":"Galderisi, U., Jori, F.P. & Giordano, A. Cell cycle regulation and neural differentiation. Oncogene 22, 5208\u20135219 (2003).","journal-title":"Oncogene"},{"key":"BFnm4296_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-62703-640-5_1","volume":"1078","author":"J Gordon","year":"2013","unstructured":"Gordon, J., Amini, S. & White, M.K. General overview of neuronal cell culture. Methods Mol. Biol. 1078, 1\u20138 (2013).","journal-title":"Methods Mol. Biol."},{"key":"BFnm4296_CR19","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/S1097-2765(02)00497-5","volume":"9","author":"W An","year":"2002","unstructured":"An, W., Palhan, V.B., Karymov, M.A., Leuba, S.H. & Roeder, R.G. Selective requirements for histone H3 and H4 N termini in p300-dependent transcriptional activation from chromatin. Mol. Cell 9, 811\u2013821 (2002).","journal-title":"Mol. Cell"},{"key":"BFnm4296_CR20","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nrd4286","volume":"13","author":"P Filippakopoulos","year":"2014","unstructured":"Filippakopoulos, P. & Knapp, S. Targeting bromodomains: epigenetic readers of lysine acetylation. Nat. Rev. Drug Discov. 13, 337\u2013356 (2014).","journal-title":"Nat. Rev. Drug Discov."},{"key":"BFnm4296_CR21","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1177\/1758834010366430","volume":"2","author":"S Gupta","year":"2010","unstructured":"Gupta, S., Takebe, N. & Lorusso, P. Targeting the Hedgehog pathway in cancer. Ther. Adv. Med. Oncol. 2, 237\u2013250 (2010).","journal-title":"Ther. Adv. Med. Oncol."},{"key":"BFnm4296_CR22","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nrc1802","volume":"6","author":"ML Whitfield","year":"2006","unstructured":"Whitfield, M.L., George, L.K., Grant, G.D. & Perou, C.M. Common markers of proliferation. Nat. Rev. Cancer 6, 99\u2013106 (2006).","journal-title":"Nat. Rev. Cancer"},{"key":"BFnm4296_CR23","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1038\/nbt.3652","volume":"34","author":"A Weiner","year":"2016","unstructured":"Weiner, A. et al. Co-ChIP enables genome-wide mapping of histone mark co-occurrence at single-molecule resolution. Nat. Biotechnol. 34, 953\u2013961 (2016).","journal-title":"Nat. Biotechnol."},{"key":"BFnm4296_CR24","doi-asserted-by":"publisher","first-page":"4958","DOI":"10.1093\/nar\/gkq244","volume":"38","author":"D Pasini","year":"2010","unstructured":"Pasini, D. et al. Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes. Nucleic Acids Res. 38, 4958\u20134969 (2010).","journal-title":"Nucleic Acids Res."},{"key":"BFnm4296_CR25","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.molcel.2013.10.030","volume":"53","author":"KJ Ferrari","year":"2014","unstructured":"Ferrari, K.J. et al. Polycomb-dependent H3K27me1 and H3K27me2 regulate active transcription and enhancer fidelity. Mol. Cell 53, 49\u201362 (2014).","journal-title":"Mol. Cell"},{"key":"BFnm4296_CR26","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/j.molcel.2008.05.007","volume":"30","author":"F Mohn","year":"2008","unstructured":"Mohn, F. et al. Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. Mol. Cell 30, 755\u2013766 (2008).","journal-title":"Mol. Cell"},{"key":"BFnm4296_CR27","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan, D. & Weinberg, R.A. Hallmarks of cancer: the next generation. Cell 144, 646\u2013674 (2011).","journal-title":"Cell"},{"key":"BFnm4296_CR28","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1038\/nrc3811","volume":"14","author":"C Jones","year":"2014","unstructured":"Jones, C. & Baker, S.J. Unique genetic and epigenetic mechanisms driving paediatric diffuse high-grade glioma. Nat. Rev. Cancer 14, 651\u2013661 (2014).","journal-title":"Nat. Rev. Cancer"},{"key":"BFnm4296_CR29","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1038\/nm0715-827a","volume":"21","author":"CS Grasso","year":"2015","unstructured":"Grasso, C.S. et al. Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nat. Med. 21, 827 (2015).","journal-title":"Nat. Med."},{"key":"BFnm4296_CR30","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1038\/nm.3952","volume":"21","author":"PK Mazur","year":"2015","unstructured":"Mazur, P.K. et al. Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma. Nat. Med. 21, 1163\u20131171 (2015).","journal-title":"Nat. Med."},{"key":"BFnm4296_CR31","doi-asserted-by":"publisher","first-page":"E2721","DOI":"10.1073\/pnas.1406722111","volume":"111","author":"J Bhadury","year":"2014","unstructured":"Bhadury, J. et al. BET and HDAC inhibitors induce similar genes and biological effects and synergize to kill in Myc-induced murine lymphoma. Proc. Natl. Acad. Sci. USA 111, E2721\u2013E2730 (2014).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm4296_CR32","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s11060-012-0973-6","volume":"110","author":"R Hashizume","year":"2012","unstructured":"Hashizume, R. et al. Characterization of a diffuse intrinsic pontine glioma cell line: implications for future investigations and treatment. J. Neurooncol. 110, 305\u2013313 (2012).","journal-title":"J. Neurooncol."},{"key":"BFnm4296_CR33","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1093\/neuonc\/not220","volume":"16","author":"S Mueller","year":"2014","unstructured":"Mueller, S. et al. Targeting Wee1 for the treatment of pediatric high-grade gliomas. Neuro-oncol. 16, 352\u2013360 (2014).","journal-title":"Neuro-oncol."},{"key":"BFnm4296_CR34","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1016\/j.cell.2015.07.042","volume":"162","author":"FX Chen","year":"2015","unstructured":"Chen, F.X. et al. PAF1, a molecular regulator of promoter-proximal pausing by RNA polymerase II. Cell 162, 1003\u20131015 (2015).","journal-title":"Cell"},{"key":"BFnm4296_CR35","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1101\/gad.246173.114","volume":"29","author":"F Chen","year":"2015","unstructured":"Chen, F., Gao, X. & Shilatifard, A. Stably paused genes revealed through inhibition of transcription initiation by the TFIIH inhibitor triptolide. Genes Dev. 29, 39\u201347 (2015).","journal-title":"Genes Dev."},{"key":"BFnm4296_CR36","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1038\/nprot.2006.98","volume":"1","author":"TI Lee","year":"2006","unstructured":"Lee, T.I., Johnstone, S.E. & Young, R.A. Chromatin immunoprecipitation and microarray-based analysis of protein location. Nat. Protoc. 1, 729\u2013748 (2006).","journal-title":"Nat. Protoc."},{"key":"BFnm4296_CR37","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger, A.M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114\u20132120 (2014).","journal-title":"Bioinformatics"},{"key":"BFnm4296_CR38","doi-asserted-by":"publisher","first-page":"R25","DOI":"10.1186\/gb-2009-10-3-r25","volume":"10","author":"B Langmead","year":"2009","unstructured":"Langmead, B., Trapnell, C., Pop, M. & Salzberg, S.L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009).","journal-title":"Genome Biol."},{"key":"BFnm4296_CR39","doi-asserted-by":"publisher","first-page":"1952","DOI":"10.1093\/bioinformatics\/btp340","volume":"25","author":"C Zang","year":"2009","unstructured":"Zang, C. et al. A clustering approach for identification of enriched domains from histone modification ChIP-Seq data. Bioinformatics 25, 1952\u20131958 (2009).","journal-title":"Bioinformatics"},{"key":"BFnm4296_CR40","doi-asserted-by":"publisher","first-page":"3246","DOI":"10.1093\/bioinformatics\/bth349","volume":"20","author":"AJ Saldanha","year":"2004","unstructured":"Saldanha, A.J. Java Treeview\u2014extensible visualization of microarray data. Bioinformatics 20, 3246\u20133248 (2004).","journal-title":"Bioinformatics"},{"key":"BFnm4296_CR41","doi-asserted-by":"publisher","first-page":"R36","DOI":"10.1186\/gb-2013-14-4-r36","volume":"14","author":"D Kim","year":"2013","unstructured":"Kim, D. et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36 (2013).","journal-title":"Genome Biol."},{"key":"BFnm4296_CR42","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","volume":"31","author":"S Anders","year":"2015","unstructured":"Anders, S., Pyl, P.T. & Huber, W. HTSeq\u2014a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166\u2013169 (2015).","journal-title":"Bioinformatics"},{"key":"BFnm4296_CR43","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson, M.D., McCarthy, D.J. & Smyth, G.K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139\u2013140 (2010).","journal-title":"Bioinformatics"},{"key":"BFnm4296_CR44","doi-asserted-by":"publisher","first-page":"3665","DOI":"10.1073\/pnas.1019736108","volume":"108","author":"KL Meerbrey","year":"2011","unstructured":"Meerbrey, K.L. et al. The pINDUCER lentiviral toolkit for inducible RNA interference in vitro and in vivo. Proc. Natl. Acad. Sci. USA 108, 3665\u20133670 (2011).","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm.4296.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm.4296","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm.4296.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T19:00:51Z","timestamp":1684436451000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm.4296"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,27]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2017,4]]}},"alternative-id":["BFnm4296"],"URL":"https:\/\/doi.org\/10.1038\/nm.4296","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,27]]},"assertion":[{"value":"30 November 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}