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Chromatin interaction maps identify Wnt responsive cis-regulatory elements coordinating Paupar-Pax6 expression in neuronal cells

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...

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Autores principales: Pavlaki, Ioanna, Shapiro, Michael, Pisignano, Giuseppina, Jones, Stephanie M. E., Telenius, Jelena, Muñoz-Descalzo, Silvia, Williams, Robert J., Hughes, Jim R., Vance, Keith W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202886/
https://www.ncbi.nlm.nih.gov/pubmed/35709096
http://dx.doi.org/10.1371/journal.pgen.1010230
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author Pavlaki, Ioanna
Shapiro, Michael
Pisignano, Giuseppina
Jones, Stephanie M. E.
Telenius, Jelena
Muñoz-Descalzo, Silvia
Williams, Robert J.
Hughes, Jim R.
Vance, Keith W.
author_facet Pavlaki, Ioanna
Shapiro, Michael
Pisignano, Giuseppina
Jones, Stephanie M. E.
Telenius, Jelena
Muñoz-Descalzo, Silvia
Williams, Robert J.
Hughes, Jim R.
Vance, Keith W.
author_sort Pavlaki, Ioanna
collection PubMed
description 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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spelling pubmed-92028862022-06-17 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. PLoS Genet Research Article 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. Public Library of Science 2022-06-16 /pmc/articles/PMC9202886/ /pubmed/35709096 http://dx.doi.org/10.1371/journal.pgen.1010230 Text en © 2022 Pavlaki et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pavlaki, Ioanna
Shapiro, Michael
Pisignano, Giuseppina
Jones, Stephanie M. E.
Telenius, Jelena
Muñoz-Descalzo, Silvia
Williams, Robert J.
Hughes, Jim R.
Vance, Keith W.
Chromatin interaction maps identify Wnt responsive cis-regulatory elements coordinating Paupar-Pax6 expression in neuronal cells
title Chromatin interaction maps identify Wnt responsive cis-regulatory elements coordinating Paupar-Pax6 expression in neuronal cells
title_full Chromatin interaction maps identify Wnt responsive cis-regulatory elements coordinating Paupar-Pax6 expression in neuronal cells
title_fullStr Chromatin interaction maps identify Wnt responsive cis-regulatory elements coordinating Paupar-Pax6 expression in neuronal cells
title_full_unstemmed Chromatin interaction maps identify Wnt responsive cis-regulatory elements coordinating Paupar-Pax6 expression in neuronal cells
title_short Chromatin interaction maps identify Wnt responsive cis-regulatory elements coordinating Paupar-Pax6 expression in neuronal cells
title_sort chromatin interaction maps identify wnt responsive cis-regulatory elements coordinating paupar-pax6 expression in neuronal cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202886/
https://www.ncbi.nlm.nih.gov/pubmed/35709096
http://dx.doi.org/10.1371/journal.pgen.1010230
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