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BAHCC1 binds H3K27me3 via a conserved BAH module to mediate gene silencing and oncogenesis.
Fan, Huitao; Lu, Jiuwei; Guo, Yiran; Li, Dongxu; Zhang, Zhi-Min; Tsai, Yi-Hsuan; Pi, Wen-Chieh; Ahn, Jeong Hyun; Gong, Weida; Xiang, Yu; Allison, David F; Geng, Huimin; He, Shenghui; Diao, Yarui; Chen, Wei-Yi; Strahl, Brian D; Cai, Ling; Song, Jikui; Wang, Gang Greg.
Afiliação
  • Fan H; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
  • Lu J; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
  • Guo Y; Department of Biochemistry, University of California, Riverside, Riverside, CA, USA.
  • Li D; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
  • Zhang ZM; Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Tsai YH; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
  • Pi WC; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
  • Ahn JH; Department of Biochemistry, University of California, Riverside, Riverside, CA, USA.
  • Gong W; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
  • Xiang Y; Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
  • Allison DF; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
  • Geng H; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
  • He S; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
  • Diao Y; Department of Cell Biology and Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, USA.
  • Chen WY; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
  • Strahl BD; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
  • Cai L; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Song J; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
  • Wang GG; Department of Genetics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
Nat Genet ; 52(12): 1384-1396, 2020 12.
Article em En | MEDLINE | ID: mdl-33139953
ABSTRACT
Trimethylated histone H3 lysine 27 (H3K27me3) regulates gene repression, cell-fate determination and differentiation. We report that a conserved bromo-adjacent homology (BAH) module of BAHCC1 (BAHCC1BAH) 'recognizes' H3K27me3 specifically and enforces silencing of H3K27me3-demarcated genes in mammalian cells. Biochemical, structural and integrated chromatin immunoprecipitation-sequencing-based analyses demonstrate that direct readout of H3K27me3 by BAHCC1 is achieved through a hydrophobic trimethyl-L-lysine-binding 'cage' formed by BAHCC1BAH, mediating colocalization of BAHCC1 and H3K27me3-marked genes. BAHCC1 is highly expressed in human acute leukemia and interacts with transcriptional corepressors. In leukemia, depletion of BAHCC1, or disruption of the BAHCC1BAH-H3K27me3 interaction, causes derepression of H3K27me3-targeted genes that are involved in tumor suppression and cell differentiation, leading to suppression of oncogenesis. In mice, introduction of a germline mutation at Bahcc1 to disrupt its H3K27me3 engagement causes partial postnatal lethality, supporting a role in development. This study identifies an H3K27me3-directed transduction pathway in mammals that relies on a conserved BAH 'reader'.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Histonas / Leucemia / Proteínas / Código das Histonas / Carcinogênese Limite: Animals / Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Histonas / Leucemia / Proteínas / Código das Histonas / Carcinogênese Limite: Animals / Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos