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PDBsum entry 4qb3
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Transcription/transcription inhibitor
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PDB id
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4qb3
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References listed in PDB file
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Key reference
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Title
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Selective chemical modulation of gene transcription favors oligodendrocyte lineage progression.
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Authors
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M.Gacias,
G.Gerona-Navarro,
A.N.Plotnikov,
G.Zhang,
L.Zeng,
J.Kaur,
G.Moy,
E.Rusinova,
Y.Rodriguez,
B.Matikainen,
A.Vincek,
J.Joshua,
P.Casaccia,
M.M.Zhou.
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Ref.
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Chem Biol, 2014,
21,
841-854.
[DOI no: ]
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PubMed id
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Abstract
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Lysine acetylation regulates gene expression through modulating protein-protein
interactions in chromatin. Chemical inhibition of acetyl-lysine binding
bromodomains of the major chromatin regulators BET (bromodomain and
extraterminal domain) proteins has been shown to effectively block cell
proliferation in cancer and inflammation. However, whether selective inhibition
of individual BET bromodomains has distinctive functional consequences remains
only partially understood. In this study, we show that selective chemical
inhibition of the first bromodomain of BET proteins using our small-molecule
inhibitor, Olinone, accelerated the progression of mouse primary oligodendrocyte
progenitors toward differentiation, whereas inhibition of both bromodomains of
BET proteins hindered differentiation. This effect was target specific, as it
was not detected in cells treated with inactive analogs and independent of any
effect on proliferation. Therefore, selective chemical modulation of individual
bromodomains, rather than use of broad-based inhibitors, may enhance
regenerative strategies in disorders characterized by myelin loss such as aging
and neurodegeneration.
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