title: Selective chemical modulation of gene transcription favors oligodendrocyte lineage progression.
abstract: 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.
authors: Departments of Neuroscience, and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors: Mar
authors: M
authors: Gacias
authors: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.|Department of Chemistry, Brooklyn College, 2900 Bedford Avenue, Room 351 NE, Brooklyn, NY 11210, USA.
authors: Guillermo
authors: G
authors: Gerona-Navarro
authors: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors: Alexander N
authors: AN
authors: Plotnikov
authors: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors: Guangtao
authors: G
authors: Zhang
authors: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors: Lei
authors: L
authors: Zeng
authors: Departments of Neuroscience, and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors: Jasbir
authors: J
authors: Kaur
authors: Departments of Neuroscience, and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors: Gregory
authors: G
authors: Moy
authors: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors: Elena
authors: E
authors: Rusinova
authors: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.|Department of Natural Sciences, Hostos Community College of CUNY, Bronx, NY 10451, USA.
authors: Yoel
authors: Y
authors: Rodriguez
authors: Departments of Neuroscience, and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors: Bridget
authors: B
authors: Matikainen
authors: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors: Adam
authors: A
authors: Vincek
authors: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors: Jennifer
authors: J
authors: Joshua
authors: Departments of Neuroscience, and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors: Patrizia
authors: P
authors: Casaccia
authors: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors: Ming-Ming
authors: MM
authors: Zhou
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000378:metabolism / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D013379:Substrate Specificity; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D000092468:Bromodomain Containing Proteins
chemical_list: D008239:Lysine; D009687:Nuclear Proteins; D054852:Small Molecule Libraries; D014157:Transcription Factors; C486694:Brd4 protein, mouse; D000092468:Bromodomain Containing Proteins