title: Lack of Rybp in Mouse Embryonic Stem Cells Impairs Cardiac Differentiation.
abstract: Ring1 and Yy1 binding protein (Rybp) has been implicated in transcriptional regulation, apoptotic signaling and as a member of the polycomb repressive complex 1, it has an important function in regulating pluripotency and differentiation of embryonic stem cells (ESCs). Earlier, we had proved that Rybp plays an essential role in mouse embryonic and central nervous system development. This work identifies Rybp, as a critical regulator of heart development. Rybp is readily detectable in the developing mouse heart from day 8.5 of embryonic development. Prominent Rybp expression persists during all embryonic stages, and Rybp marks differentiated cell types of the heart. By utilizing rybp null ESCs in an in vitro cardiac differentiation assay, we found that rybp null ESCs do not form rhythmically beating cardiomyocytes (CMCs). Gene expression profiles revealed a downregulation of cardiac terminal and upregulation of germline-specific markers in the rybp null CMCs. Furthermore, transcriptome analysis uncovered a number of novel candidate target genes regulated by Rybp. Among these are several that are important in cardiac development and contractility such as Plagl1, Isl1, and Tnnt2. Importantly, forced expression of rybp in rybp-deficient ESCs by a lentiviral vector was able to rescue the mutant phenotype. Our data provide evidence for a previously unrecognized function of Rybp in heart development and point out the importance of germ cell lineage gene silencing during somatic differentiation.
authors.affiliation: 1 BioTalentum Ltd. , Gödöllö, Hungary .
authors.forename: Olga
authors.initials: O
authors.lastname: Ujhelly
authors.affiliation: 2 Institute of Genetics , Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary .
authors.forename: Viktoria
authors.initials: V
authors.lastname: Szabo
authors.affiliation: 2 Institute of Genetics , Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary .
authors.forename: Gergo
authors.initials: G
authors.lastname: Kovacs
authors.affiliation: 2 Institute of Genetics , Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary .
authors.forename: Flora
authors.initials: F
authors.lastname: Vajda
authors.affiliation: 3 Laboratory for Functional Genome Analysis (LAFUGA), Gene Center , LMU Munich, Munich, Germany .
authors.forename: Sylvia
authors.initials: S
authors.lastname: Mallok
authors.affiliation: 4 Department of Pharmacology and Pharmacotherapy, University of Szeged , Szeged, Hungary .
authors.forename: Janos
authors.initials: J
authors.lastname: Prorok
authors.affiliation: 5 MTA-SZTE Research Group of Cardiovascular Pharmacology , Szeged, Hungary .
authors.forename: Karoly
authors.initials: K
authors.lastname: Acsai
authors.affiliation: 6 Institute of Biophysics , Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary .
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Hegedus
authors.affiliation: 3 Laboratory for Functional Genome Analysis (LAFUGA), Gene Center , LMU Munich, Munich, Germany .
authors.forename: Stefan
authors.initials: S
authors.lastname: Krebs
authors.affiliation: 1 BioTalentum Ltd. , Gödöllö, Hungary .|7 Molecular Animal Biotechnology Laboratory, Szent Istvan University , Gödöllö, Hungary .
authors.forename: Andras
authors.initials: A
authors.lastname: Dinnyes
authors.affiliation: 2 Institute of Genetics , Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary .
authors.forename: Melinda Katalin
authors.initials: MK
authors.lastname: Pirity
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D016147:Genes, Tumor Suppressor; D006321:Heart / Q000196:embryology*; D060850:LIM-Homeodomain Proteins / Q000235:genetics; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology*; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology*; D038081:Organogenesis / Q000235:genetics*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D020107:Troponin T / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D060850:LIM-Homeodomain Proteins; C498423:Plagl1 protein, mouse; D012097:Repressor Proteins; C120616:Rybp protein, mouse; D014157:Transcription Factors; D020107:Troponin T; C063843:insulin gene enhancer binding protein Isl-1; D063150:Polycomb Repressive Complex 1