PT  - JOURNAL ARTICLE
AU  - Hass, Matthew R.
AU  - Brisette, Daniel
AU  - Parameswaran, Sreeja
AU  - Pujato, Mario
AU  - Donmez, Omer
AU  - Kottyan, Leah C.
AU  - Weirauch, Matthew T.
AU  - Kopan, Raphael
TI  - Runx1 Shapes the Chromatin Landscape Via a Cascade of Direct and Indirect Targets
AID  - 10.1101/2020.09.25.313767
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.25.313767
4099  - http://biorxiv.org/content/early/2020/09/26/2020.09.25.313767.short
4100  - http://biorxiv.org/content/early/2020/09/26/2020.09.25.313767.full
AB  - 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 an embryonic kidney-derived cell (mK4) results in large-scale genome-wide changes to chromatin accessibility and gene expression. Open chromatin regions near down-regulated loci are enriched for Runx sites, remain bound by Runx2, but lose chromatin accessibility and expression in Runx1 knockout cells. 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. These data confirm that Runx1 activity is uniquely needed to maintain open chromatin at many loci, and demonstrate that genome-scale derepression is an indirect consequence of losing Runx1-dependent Zeb expression.Competing Interest StatementThe authors have declared no competing interest.