Journal
CELL REPORTS
Volume 38, Issue 11, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2022.110524
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Funding
- NICHD [R01HD079682]
- NINDS [R01NS100897]
- New York University
- New York Genome Center startup funds, National Institutes of Health (NIH) /National Human Genome Research Institute [R00HG008171, DP2HG010099]
- NIH/National Cancer Institute [R01CA218668]
- De-fense Advanced Research Projects Agency [D18AP00053]
- Sid-ney Kimmel Foundation
- Melanoma Research Alliance
- Cancer Research Institute
- Brain and Behavior Foundation
- CBIOS training grant from NIGMS [T32GM102057]
- NIGMS [R01GM125722]
- MDC-NYU exchange program
- Simons Foundation
- Tri-Institutional Stem Cell Initiative by the Starr Foundation (Tri-SCI)
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The transcription factors ZBTB11 and ZFP131 are essential for maintaining pluripotency in embryonic stem cells. They repress the premature expression of pro-differentiation genes, preventing the loss of pluripotency.
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.
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