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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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-06-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009574&type=printable |
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| _version_ | 1850042428910731264 |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-a61e659e34d045a0b33e892800ee2cb9 |
| institution | DOAJ |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2021-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-a61e659e34d045a0b33e892800ee2cb92025-08-20T02:55:32ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-06-01176e100957410.1371/journal.pgen.1009574Runx1 shapes the chromatin landscape via a cascade of direct and indirect targets.Matthew R HassDaniel BrissetteSreeja ParameswaranMario PujatoOmer DonmezLeah C KottyanMatthew T WeirauchRaphael KopanRunt-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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009574&type=printable |
| spellingShingle | 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. PLoS Genetics |
| title | 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_short | 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 |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009574&type=printable |
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