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CHD4 and SMYD1 repress common transcriptional programs in the developing heart.
Shi, Wei; Wasson, Lauren K; Dorr, Kerry M; Robbe, Zachary L; Wilczewski, Caralynn M; Hepperla, Austin J; Davis, Ian J; Seidman, Christine E; Seidman, Jonathan G; Conlon, Frank L.
Afiliación
  • Shi W; Department of Biology and Genetics, McAllister Heart Institute, UNC-Chapel Hill, Chapel Hill, NC 27599, USA.
  • Wasson LK; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Dorr KM; Department of Medicine and Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Robbe ZL; Department of Biology and Genetics, McAllister Heart Institute, UNC-Chapel Hill, Chapel Hill, NC 27599, USA.
  • Wilczewski CM; Department of Biology and Genetics, McAllister Heart Institute, UNC-Chapel Hill, Chapel Hill, NC 27599, USA.
  • Hepperla AJ; Department of Biology and Genetics, McAllister Heart Institute, UNC-Chapel Hill, Chapel Hill, NC 27599, USA.
  • Davis IJ; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Seidman CE; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Seidman JG; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Conlon FL; Department of Medicine and Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Development ; 151(8)2024 Apr 15.
Article en En | MEDLINE | ID: mdl-38619323
ABSTRACT
Regulation of chromatin states is essential for proper temporal and spatial gene expression. Chromatin states are modulated by remodeling complexes composed of components that have enzymatic activities. CHD4 is the catalytic core of the nucleosome remodeling and deacetylase (NuRD) complex, which represses gene transcription. However, it remains to be determined how CHD4, a ubiquitous enzyme that remodels chromatin structure, functions in cardiomyocytes to maintain heart development. In particular, whether other proteins besides the NuRD components interact with CHD4 in the heart is controversial. Using quantitative proteomics, we identified that CHD4 interacts with SMYD1, a striated muscle-restricted histone methyltransferase that is essential for cardiomyocyte differentiation and cardiac morphogenesis. Comprehensive transcriptomic and chromatin accessibility studies of Smyd1 and Chd4 null embryonic mouse hearts revealed that SMYD1 and CHD4 repress a group of common genes and pathways involved in glycolysis, response to hypoxia, and angiogenesis. Our study reveals a mechanism by which CHD4 functions during heart development, and a previously uncharacterized mechanism regarding how SMYD1 represses cardiac transcription in the developing heart.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / ADN Helicasas / Regulación del Desarrollo de la Expresión Génica / Miocitos Cardíacos / Proteínas de Unión al ADN / Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2 / Corazón Límite: Animals / Humans Idioma: En Revista: Development Asunto de la revista: BIOLOGIA / EMBRIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / ADN Helicasas / Regulación del Desarrollo de la Expresión Génica / Miocitos Cardíacos / Proteínas de Unión al ADN / Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2 / Corazón Límite: Animals / Humans Idioma: En Revista: Development Asunto de la revista: BIOLOGIA / EMBRIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido