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Alternative splicing of a chromatin modifier alters the transcriptional regulatory programs of stem cell maintenance and neuronal differentiation.
Nazim, Mohammad; Lin, Chia-Ho; Feng, An-Chieh; Xiao, Wen; Yeom, Kyu-Hyeon; Li, Mulin; Daly, Allison E; Tan, Xianglong; Vu, Ha; Ernst, Jason; Carey, Michael F; Smale, Stephen T; Black, Douglas L.
Afiliación
  • Nazim M; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Lin CH; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Feng AC; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Xiao W; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Yeom KH; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Li M; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Daly AE; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Tan X; Department of Biological Chemistry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Vu H; Department of Biological Chemistry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Ernst J; Department of Biological Chemistry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Carey MF; Department of Biological Chemistry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Smale ST; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Black DL; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. Electronic address: dougb@microbio.ucla.edu.
Cell Stem Cell ; 31(5): 754-771.e6, 2024 May 02.
Article en En | MEDLINE | ID: mdl-38701759
ABSTRACT
Development of embryonic stem cells (ESCs) into neurons requires intricate regulation of transcription, splicing, and translation, but how these processes interconnect is not understood. We found that polypyrimidine tract binding protein 1 (PTBP1) controls splicing of DPF2, a subunit of BRG1/BRM-associated factor (BAF) chromatin remodeling complexes. Dpf2 exon 7 splicing is inhibited by PTBP1 to produce the DPF2-S isoform early in development. During neuronal differentiation, loss of PTBP1 allows exon 7 inclusion and DPF2-L expression. Different cellular phenotypes and gene expression programs were induced by these alternative DPF2 isoforms. We identified chromatin binding sites enriched for each DPF2 isoform, as well as sites bound by both. In ESC, DPF2-S preferential sites were bound by pluripotency factors. In neuronal progenitors, DPF2-S sites were bound by nuclear factor I (NFI), while DPF2-L sites were bound by CCCTC-binding factor (CTCF). DPF2-S sites exhibited enhancer modifications, while DPF2-L sites showed promoter modifications. Thus, alternative splicing redirects BAF complex targeting to impact chromatin organization during neuronal development.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Factores de Transcripción / Cromatina / Diferenciación Celular / Empalme Alternativo / Proteína de Unión al Tracto de Polipirimidina / Ribonucleoproteínas Nucleares Heterogéneas / Neuronas Límite: Animals / Humans Idioma: En Revista: Cell Stem Cell Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Factores de Transcripción / Cromatina / Diferenciación Celular / Empalme Alternativo / Proteína de Unión al Tracto de Polipirimidina / Ribonucleoproteínas Nucleares Heterogéneas / Neuronas Límite: Animals / Humans Idioma: En Revista: Cell Stem Cell Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos