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Title: Chromatin interaction maps identify Wnt responsive cis-regulatory elements coordinating Paupar-Pax6 expression in neuronal cells
Authors: Pavlaki, Ioanna
Shapiro, Michael
Pisignano, Giuseppina
Jones, Stephanie M. E.
Telenius, Jelena
Muñoz Descalzo, Silvia 
Williams, Robert J.
Hughes, Jim R.
Vance, Keith W.
Editors: D’Orso, Ivan
UNESCO Clasification: 32 Ciencias médicas
320102 Genética clínica
Keywords: Chromatin
Transcription factors
Neuronal differentiation
Long non-coding RNA, et al
Issue Date: 2022
Journal: PLoS Genetics 
Abstract: 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 ner- vous system and are predicted to act together to regulate neuronal development and func- tion. 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.
ISSN: 1553-7404
DOI: 10.1371/journal.pgen.1010230
Source: PLoS Genetics [ISSN 1553-7404], v. 18 (6), e1010230, (2022)
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