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@ARTICLE{Gallo:126558,
author = {M. Gallo and F. J. Coutinho and R. J. Vanner and T. Gayden
and S. C. Mack and A. Murison and M. Remke and R. Li and N.
Takayama and K. Desai and L. Lee and X. Lan and N. I. Park
and D. Barsyte-Lovejoy and D. Smil and D. Sturm$^*$ and M.
M. Kushida and R. Head and M. D. Cusimano and M. Bernstein
and I. D. Clarke and J. E. Dick and S. Pfister$^*$ and J. N.
Rich and C. H. Arrowsmith and M. D. Taylor and N. Jabado and
D. P. Bazett-Jones and M. Lupien and P. B. Dirks},
title = {{MLL}5 {O}rchestrates a {C}ancer {S}elf-{R}enewal {S}tate
by {R}epressing the {H}istone {V}ariant {H}3.3 and
{G}lobally {R}eorganizing {C}hromatin.},
journal = {Cancer cell},
volume = {28},
number = {6},
issn = {1535-6108},
address = {Cambridge, Mass.},
publisher = {Cell Press},
reportid = {DKFZ-2017-02586},
pages = {715 - 729},
year = {2015},
abstract = {Mutations 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.},
keywords = {Antineoplastic Agents (NLM Chemicals) / DNA-Binding
Proteins (NLM Chemicals) / Histones (NLM Chemicals) / MLL5
protein, human (NLM Chemicals)},
cin = {B062},
ddc = {610},
cid = {I:(DE-He78)B062-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26626085},
doi = {10.1016/j.ccell.2015.10.005},
url = {https://inrepo02.dkfz.de/record/126558},
}