A novel RNA-mediated mechanism causing down-regulation of insulating promoter interactions in human embryonic stem cells

Abstract The genome-wide promoter interactome is primarily maintained and regulated by architectural proteins such as CTCF and cohesin. However, some studies suggest a role for non-coding RNAs (ncRNAs) in this process. We aimed to characterise the regulatory role of RNA-mediated promoter interaction...

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Auteurs principaux:	Yingjuan Liu, Simon G. Williams, Hayden R. Jones, Bernard D. Keavney, Mun-Kit Choy
Format:	article
Langue:	EN
Publié:	Nature Portfolio 2021
Sujets:	Medicine R Science Q
Accès en ligne:	https://doaj.org/article/e549fe2048b642deb926b19e627cea3f
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spelling	oai:doaj.org-article:e549fe2048b642deb926b19e627cea3f2021-12-05T12:14:45ZA novel RNA-mediated mechanism causing down-regulation of insulating promoter interactions in human embryonic stem cells10.1038/s41598-021-02373-12045-2322https://doaj.org/article/e549fe2048b642deb926b19e627cea3f2021-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02373-1https://doaj.org/toc/2045-2322Abstract The genome-wide promoter interactome is primarily maintained and regulated by architectural proteins such as CTCF and cohesin. However, some studies suggest a role for non-coding RNAs (ncRNAs) in this process. We aimed to characterise the regulatory role of RNA-mediated promoter interactions in the control of gene expression. We integrated genome-wide datasets of RNA-chromatin and promoter-genome interactions in human embryonic stem cells (hESCs) to identify putative RNA-mediated promoter interactions. We discovered that CTCF sites were enriched in RNA-PIRs (promoter interacting regions co-localising with RNA-chromatin interaction sites) and genes interacting with RNA-PIRs containing CTCF sites showed higher expression levels. One of the long noncoding RNAs (lncRNAs) expressed in hESCs, Syntaxin 18-Antisense 1 (STX18-AS1), appeared to be involved in an insulating promoter interaction with the neighbouring gene, MSX1. By knocking down STX18-AS1, the MSX1 promoter-PIR interaction was intensified and the target gene (MSX1) expression was down-regulated. Conversely, reduced MSX1 promoter-PIR interactions, resulting from CRISPR-Cas9 deletion of the PIR, increased the expression of MSX1. We conclude that STX18-AS1 RNA antagonised local CTCF-mediated insulating promoter interactions to augment gene expression. Such down-regulation of the insulating promoter interactions by this novel mechanism may explain the higher expression of genes interacting with RNA-PIRs linked to CTCF sites.Yingjuan LiuSimon G. WilliamsHayden R. JonesBernard D. KeavneyMun-Kit ChoyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yingjuan Liu Simon G. Williams Hayden R. Jones Bernard D. Keavney Mun-Kit Choy A novel RNA-mediated mechanism causing down-regulation of insulating promoter interactions in human embryonic stem cells
description	Abstract The genome-wide promoter interactome is primarily maintained and regulated by architectural proteins such as CTCF and cohesin. However, some studies suggest a role for non-coding RNAs (ncRNAs) in this process. We aimed to characterise the regulatory role of RNA-mediated promoter interactions in the control of gene expression. We integrated genome-wide datasets of RNA-chromatin and promoter-genome interactions in human embryonic stem cells (hESCs) to identify putative RNA-mediated promoter interactions. We discovered that CTCF sites were enriched in RNA-PIRs (promoter interacting regions co-localising with RNA-chromatin interaction sites) and genes interacting with RNA-PIRs containing CTCF sites showed higher expression levels. One of the long noncoding RNAs (lncRNAs) expressed in hESCs, Syntaxin 18-Antisense 1 (STX18-AS1), appeared to be involved in an insulating promoter interaction with the neighbouring gene, MSX1. By knocking down STX18-AS1, the MSX1 promoter-PIR interaction was intensified and the target gene (MSX1) expression was down-regulated. Conversely, reduced MSX1 promoter-PIR interactions, resulting from CRISPR-Cas9 deletion of the PIR, increased the expression of MSX1. We conclude that STX18-AS1 RNA antagonised local CTCF-mediated insulating promoter interactions to augment gene expression. Such down-regulation of the insulating promoter interactions by this novel mechanism may explain the higher expression of genes interacting with RNA-PIRs linked to CTCF sites.
format	article
author	Yingjuan Liu Simon G. Williams Hayden R. Jones Bernard D. Keavney Mun-Kit Choy
author_facet	Yingjuan Liu Simon G. Williams Hayden R. Jones Bernard D. Keavney Mun-Kit Choy
author_sort	Yingjuan Liu
title	A novel RNA-mediated mechanism causing down-regulation of insulating promoter interactions in human embryonic stem cells
title_short	A novel RNA-mediated mechanism causing down-regulation of insulating promoter interactions in human embryonic stem cells
title_full	A novel RNA-mediated mechanism causing down-regulation of insulating promoter interactions in human embryonic stem cells
title_fullStr	A novel RNA-mediated mechanism causing down-regulation of insulating promoter interactions in human embryonic stem cells
title_full_unstemmed	A novel RNA-mediated mechanism causing down-regulation of insulating promoter interactions in human embryonic stem cells
title_sort	novel rna-mediated mechanism causing down-regulation of insulating promoter interactions in human embryonic stem cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e549fe2048b642deb926b19e627cea3f
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A novel RNA-mediated mechanism causing down-regulation of insulating promoter interactions in human embryonic stem cells

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