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The BTB transcription factors ZBTB11 and ZFP131 maintain pluripotency by repressing pro-differentiation genes

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Item Type:Article
Title:The BTB transcription factors ZBTB11 and ZFP131 maintain pluripotency by repressing pro-differentiation genes
Creators Name:Garipler, G. and Lu, C. and Morrissey, Al. and Lopez-Zepeda, L.S. and Pei, Y. and Vidal, S.E. and Zen Petisco Fiore, A.P. and Aydin, B. and Stadtfeld, M. and Ohler, U. and Mahony, S. and Sanjana, N.E. and Mazzoni, E.O.
Abstract:In pluripotent cells, a delicate activation-repression balance maintains pro-differentiation genes ready for rapid activation. The identity of transcription factors (TFs) that specifically repress pro-differentiation genes remains obscure. By targeting ∼1,700 TFs with CRISPR loss-of-function screen, we found that ZBTB11 and ZFP131 are required for embryonic stem cell (ESC) pluripotency. ESCs without ZBTB11 or ZFP131 lose colony morphology, reduce proliferation rate, and upregulate transcription of genes associated with three germ layers. ZBTB11 and ZFP131 bind proximally to pro-differentiation genes. ZBTB11 or ZFP131 loss leads to an increase in H3K4me3, negative elongation factor (NELF) complex release, and concomitant transcription at associated genes. Together, our results suggest that ZBTB11 and ZFP131 maintain pluripotency by preventing premature expression of pro-differentiation genes and present a generalizable framework to maintain cellular potency.
Keywords:Pluripotency, Embryonic Stem Cells, CRISPR Screen, Transcription Factors, Differentiation, Poised Genes
Source:Cell Reports
ISSN:2211-1247
Publisher:Cell Press / Elsevier
Volume:38
Number:11
Page Range:110524
Date:15 March 2022
Official Publication:https://doi.org/10.1016/j.celrep.2022.110524
PubMed:View item in PubMed

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