Runx1 shapes the chromatin landscape via a cascade of direct and indirect targets.

Runt-related transcription factor 1 (Runx1) can act as both an activator and a repressor. Here we show that CRISPR-mediated deletion of Runx1 in mouse metanephric mesenchyme-derived mK4 cells results in large-scale genome-wide changes to chromatin accessibility and gene expression. Open chromatin re...

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Autores principales:	Matthew R Hass, Daniel Brissette, Sreeja Parameswaran, Mario Pujato, Omer Donmez, Leah C Kottyan, Matthew T Weirauch, Raphael Kopan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/a61e659e34d045a0b33e892800ee2cb9
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id	oai:doaj.org-article:a61e659e34d045a0b33e892800ee2cb9
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spelling	oai:doaj.org-article:a61e659e34d045a0b33e892800ee2cb92021-12-02T20:02:42ZRunx1 shapes the chromatin landscape via a cascade of direct and indirect targets.1553-73901553-740410.1371/journal.pgen.1009574https://doaj.org/article/a61e659e34d045a0b33e892800ee2cb92021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009574https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Runt-related transcription factor 1 (Runx1) can act as both an activator and a repressor. Here we show that CRISPR-mediated deletion of Runx1 in mouse metanephric mesenchyme-derived mK4 cells results in large-scale genome-wide changes to chromatin accessibility and gene expression. Open chromatin regions near down-regulated loci enriched for Runx sites in mK4 cells lose chromatin accessibility in Runx1 knockout cells, despite remaining Runx2-bound. Unexpectedly, regions near upregulated genes are depleted of Runx sites and are instead enriched for Zeb transcription factor binding sites. Re-expressing Zeb2 in Runx1 knockout cells restores suppression, and CRISPR mediated deletion of Zeb1 and Zeb2 phenocopies the gained expression and chromatin accessibility changes seen in Runx1KO due in part to subsequent activation of factors like Grhl2. These data confirm that Runx1 activity is uniquely needed to maintain open chromatin at many loci, and demonstrate that Zeb proteins are required and sufficient to maintain Runx1-dependent genome-scale repression.Matthew R HassDaniel BrissetteSreeja ParameswaranMario PujatoOmer DonmezLeah C KottyanMatthew T WeirauchRaphael KopanPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 6, p e1009574 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Matthew R Hass Daniel Brissette Sreeja Parameswaran Mario Pujato Omer Donmez Leah C Kottyan Matthew T Weirauch Raphael Kopan Runx1 shapes the chromatin landscape via a cascade of direct and indirect targets.
description	Runt-related transcription factor 1 (Runx1) can act as both an activator and a repressor. Here we show that CRISPR-mediated deletion of Runx1 in mouse metanephric mesenchyme-derived mK4 cells results in large-scale genome-wide changes to chromatin accessibility and gene expression. Open chromatin regions near down-regulated loci enriched for Runx sites in mK4 cells lose chromatin accessibility in Runx1 knockout cells, despite remaining Runx2-bound. Unexpectedly, regions near upregulated genes are depleted of Runx sites and are instead enriched for Zeb transcription factor binding sites. Re-expressing Zeb2 in Runx1 knockout cells restores suppression, and CRISPR mediated deletion of Zeb1 and Zeb2 phenocopies the gained expression and chromatin accessibility changes seen in Runx1KO due in part to subsequent activation of factors like Grhl2. These data confirm that Runx1 activity is uniquely needed to maintain open chromatin at many loci, and demonstrate that Zeb proteins are required and sufficient to maintain Runx1-dependent genome-scale repression.
format	article
author	Matthew R Hass Daniel Brissette Sreeja Parameswaran Mario Pujato Omer Donmez Leah C Kottyan Matthew T Weirauch Raphael Kopan
author_facet	Matthew R Hass Daniel Brissette Sreeja Parameswaran Mario Pujato Omer Donmez Leah C Kottyan Matthew T Weirauch Raphael Kopan
author_sort	Matthew R Hass
title	Runx1 shapes the chromatin landscape via a cascade of direct and indirect targets.
title_short	Runx1 shapes the chromatin landscape via a cascade of direct and indirect targets.
title_full	Runx1 shapes the chromatin landscape via a cascade of direct and indirect targets.
title_fullStr	Runx1 shapes the chromatin landscape via a cascade of direct and indirect targets.
title_full_unstemmed	Runx1 shapes the chromatin landscape via a cascade of direct and indirect targets.
title_sort	runx1 shapes the chromatin landscape via a cascade of direct and indirect targets.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/a61e659e34d045a0b33e892800ee2cb9
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Runx1 shapes the chromatin landscape via a cascade of direct and indirect targets.

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