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Cooperative insulation of regulatory domains by CTCF-dependent physical insulation and promoter competition.
Ealo, Thais; Sanchez-Gaya, Victor; Respuela, Patricia; Muñoz-San Martín, María; Martin-Batista, Elva; Haro, Endika; Rada-Iglesias, Alvaro.
Afiliación
  • Ealo T; Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC/Universidad de Cantabria, Santander, Spain.
  • Sanchez-Gaya V; Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC/Universidad de Cantabria, Santander, Spain. victor.sanchezgaya@unican.es.
  • Respuela P; Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC/Universidad de Cantabria, Santander, Spain.
  • Muñoz-San Martín M; Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC/Universidad de Cantabria, Santander, Spain.
  • Martin-Batista E; Service of Neurology, University Hospital Marqués de Valdecilla, Universidad de Cantabria and IDIVAL, Santander, Spain.
  • Haro E; Centro de Biología Molecular Severo Ochoa (CBMSO), CSIC-UAM, Madrid, Spain.
  • Rada-Iglesias A; Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC/Universidad de Cantabria, Santander, Spain. endika.haro@unican.es.
Nat Commun ; 15(1): 7258, 2024 Aug 23.
Article en En | MEDLINE | ID: mdl-39179577
ABSTRACT
The specificity of gene expression during development requires the insulation of regulatory domains to avoid inappropriate enhancer-gene interactions. In vertebrates, this insulator function is mostly attributed to clusters of CTCF sites located at topologically associating domain (TAD) boundaries. However, TAD boundaries allow some physical crosstalk across regulatory domains, which is at odds with the specific and precise expression of developmental genes. Here we show that developmental genes and nearby clusters of CTCF sites cooperatively foster the robust insulation of regulatory domains. By genetically dissecting a couple of representative loci in mouse embryonic stem cells, we show that CTCF sites prevent undesirable enhancer-gene contacts (i.e. physical insulation), while developmental genes preferentially contribute to regulatory insulation through non-structural mechanisms involving promoter competition rather than enhancer blocking. Overall, our work provides important insights into the insulation of regulatory domains, which in turn might help interpreting the pathological consequences of certain structural variants.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Elementos de Facilitación Genéticos / Regiones Promotoras Genéticas / Células Madre Embrionarias de Ratones / Factor de Unión a CCCTC Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Elementos de Facilitación Genéticos / Regiones Promotoras Genéticas / Células Madre Embrionarias de Ratones / Factor de Unión a CCCTC Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido