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000126558 1001_ $$aGallo, Marco$$b0
000126558 245__ $$aMLL5 Orchestrates a Cancer Self-Renewal State by Repressing the Histone Variant H3.3 and Globally Reorganizing Chromatin.
000126558 260__ $$aCambridge, Mass.$$bCell Press$$c2015
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000126558 520__ $$aMutations in the histone 3 variant H3.3 have been identified in one-third of pediatric glioblastomas (GBMs), but not in adult tumors. Here we show that H3.3 is a dynamic determinant of functional properties in adult GBM. H3.3 is repressed by mixed lineage leukemia 5 (MLL5) in self-renewing GBM cells. MLL5 is a global epigenetic repressor that orchestrates reorganization of chromatin structure by punctuating chromosomes with foci of compacted chromatin, favoring tumorigenic and self-renewing properties. Conversely, H3.3 antagonizes self-renewal and promotes differentiation. We exploited these epigenetic states to rationally identify two small molecules that effectively curb cancer stem cell properties in a preclinical model. Our work uncovers a role for MLL5 and H3.3 in maintaining self-renewal hierarchies in adult GBM.
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000126558 650_7 $$2NLM Chemicals$$aAntineoplastic Agents
000126558 650_7 $$2NLM Chemicals$$aDNA-Binding Proteins
000126558 650_7 $$2NLM Chemicals$$aHistones
000126558 650_7 $$2NLM Chemicals$$aMLL5 protein, human
000126558 7001_ $$aCoutinho, Fiona J$$b1
000126558 7001_ $$aVanner, Robert J$$b2
000126558 7001_ $$aGayden, Tenzin$$b3
000126558 7001_ $$aMack, Stephen C$$b4
000126558 7001_ $$aMurison, Alex$$b5
000126558 7001_ $$0P:(DE-HGF)0$$aRemke, Marc$$b6
000126558 7001_ $$aLi, Ren$$b7
000126558 7001_ $$aTakayama, Naoya$$b8
000126558 7001_ $$aDesai, Kinjal$$b9
000126558 7001_ $$aLee, Lilian$$b10
000126558 7001_ $$aLan, Xiaoyang$$b11
000126558 7001_ $$aPark, Nicole I$$b12
000126558 7001_ $$aBarsyte-Lovejoy, Dalia$$b13
000126558 7001_ $$aSmil, David$$b14
000126558 7001_ $$0P:(DE-He78)a46a5b2a871859c8e2d63d2f8c666807$$aSturm, Dominik$$b15$$udkfz
000126558 7001_ $$aKushida, Michelle M$$b16
000126558 7001_ $$aHead, Renee$$b17
000126558 7001_ $$aCusimano, Michael D$$b18
000126558 7001_ $$aBernstein, Mark$$b19
000126558 7001_ $$aClarke, Ian D$$b20
000126558 7001_ $$aDick, John E$$b21
000126558 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b22$$udkfz
000126558 7001_ $$aRich, Jeremy N$$b23
000126558 7001_ $$aArrowsmith, Cheryl H$$b24
000126558 7001_ $$aTaylor, Michael D$$b25
000126558 7001_ $$aJabado, Nada$$b26
000126558 7001_ $$aBazett-Jones, David P$$b27
000126558 7001_ $$aLupien, Mathieu$$b28
000126558 7001_ $$aDirks, Peter B$$b29
000126558 773__ $$0PERI:(DE-600)2074034-7$$a10.1016/j.ccell.2015.10.005$$gVol. 28, no. 6, p. 715 - 729$$n6$$p715 - 729$$tCancer cell$$v28$$x1535-6108$$y2015
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