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Chromatin interaction maps identify Wnt responsive cis-regulatory elements coordinating Paupar-Pax6 expression in neuronal cells.
Pavlaki, Ioanna; Shapiro, Michael; Pisignano, Giuseppina; Jones, Stephanie M E; Telenius, Jelena; Muñoz-Descalzo, Silvia; Williams, Robert J; Hughes, Jim R; Vance, Keith W.
Afiliación
  • Pavlaki I; Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
  • Shapiro M; Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
  • Pisignano G; The Francis Crick Institute, London, United Kingdom.
  • Jones SME; Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
  • Telenius J; Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
  • Muñoz-Descalzo S; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
  • Williams RJ; Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
  • Hughes JR; Instituto Universitario de Investigaciones Biomédicas y Sanitarias, Universidad Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
  • Vance KW; Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
PLoS Genet ; 18(6): e1010230, 2022 06.
Article en En | MEDLINE | ID: mdl-35709096
Central nervous system-expressed long non-coding RNAs (lncRNAs) are often located in the genome close to protein coding genes involved in transcriptional control. Such lncRNA-protein coding gene pairs are frequently temporally and spatially co-expressed in the nervous system and are predicted to act together to regulate neuronal development and function. Although some of these lncRNAs also bind and modulate the activity of the encoded transcription factors, the regulatory mechanisms controlling co-expression of neighbouring lncRNA-protein coding genes remain unclear. Here, we used high resolution NG Capture-C to map the cis-regulatory interaction landscape of the key neuro-developmental Paupar-Pax6 lncRNA-mRNA locus. The results define chromatin architecture changes associated with high Paupar-Pax6 expression in neurons and identify both promoter selective as well as shared cis-regulatory-promoter interactions involved in regulating Paupar-Pax6 co-expression. We discovered that the TCF7L2 transcription factor, a regulator of chromatin architecture and major effector of the Wnt signalling pathway, binds to a subset of these candidate cis-regulatory elements to coordinate Paupar and Pax6 co-expression. We describe distinct roles for Paupar in Pax6 expression control and show that the Paupar DNA locus contains a TCF7L2 bound transcriptional silencer whilst the Paupar transcript can act as an activator of Pax6. Our work provides important insights into the chromatin interactions, signalling pathways and transcription factors controlling co-expression of adjacent lncRNAs and protein coding genes in the brain.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Largo no Codificante Tipo de estudio: Prognostic_studies Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Largo no Codificante Tipo de estudio: Prognostic_studies Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos