title: Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis.
abstract: Many transcription factors regulate specific temporal-spatial events during cardiac differentiation; however, the mechanisms that regulate such events are largely unknown. Using a modified subtractive hybridization method to identify specific genes that influence early cardiac development, we found that Bop is expressed specifically in cardiac and skeletal muscle precursors before differentiation of these lineages. Bop encodes a protein containing MYND and SET domains, which have been shown to regulate transcription by mediating distinct chromatin modifications. We show that m-Bop is a histone deacetylase-dependent transcriptional repressor. Targeted deletion of Bop in mice disrupted maturation of ventricular cardiomyocytes and interfered with formation of the right ventricle. Normal expression of Hand2, a transcription factor essential for right ventricular development, in cardiomyocyte precursors is dependent upon m-Bop. These results indicate that m-Bop is essential for cardiomyocyte differentiation and cardiac morphogenesis.
authors.affiliation: Section of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA. gottlieb@uts.cc.utexas.edu
authors.forename: Paul D
authors.initials: PD
authors.lastname: Gottlieb
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Pierce
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Sims
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamagishi
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Weihe
authors.forename: June V
authors.initials: JV
authors.lastname: Harriss
authors.forename: Shanna D
authors.initials: SD
authors.lastname: Maika
authors.forename: William A
authors.initials: WA
authors.lastname: Kuziel
authors.forename: Heather L
authors.initials: HL
authors.lastname: King
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakagawa
authors.forename: Deepak
authors.initials: D
authors.lastname: Srivastava
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002642:Chick Embryo; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D006321:Heart / Q000196:embryology / Q000254:growth & development; D006330:Heart Defects, Congenital / Q000196:embryology / Q000235:genetics; D006655:Histone Deacetylases / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D012097:Repressor Proteins; C096485:Smyd1 protein, mouse; D014157:Transcription Factors; D006655:Histone Deacetylases