@article{00c041cb64784623812ec984a5db24c3,
title = "The BTB transcription factors ZBTB11 and ZFP131 maintain pluripotency by repressing pro-differentiation genes",
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.",
author = "G{\"o}rkem Garipler and Congyi Lu and Alexis Morrissey and Lopez-Zepeda, {Lorena S.} and Yingzhen Pei and Vidal, {Simon E.} and {Zen Petisco Fiore}, {Ana Paula} and Beg{\"u}m Aydin and Matthias Stadtfeld and Uwe Ohler and Shaun Mahony and Sanjana, {Neville E.} and Mazzoni, {Esteban O.}",
note = "Funding Information: This work was supported by the NICHD ( R01HD079682 ) and NINDS R01NS100897 to E.O.M. N.E.S. is supported by New York University and New York Genome Center startup funds, National Institutes of Health (NIH)/ National Human Genome Research Institute (grant nos. R00HG008171 and DP2HG010099 ), NIH / National Cancer Institute (grant no. R01CA218668 ), Defense Advanced Research Projects Agency (grant no. D18AP00053 ), the Sidney Kimmel Foundation , the Melanoma Research Alliance , the Cancer Research Institute , and the Brain and Behavior Foundation . A.M. is supported by the CBIOS training grant from NIGMS ( T32GM102057 ). The Mahony lab is supported by NIGMS ( R01GM125722 ) to S.M. L.S.L.-Z. is supported by the MDC -NYU exchange program. M.S. is supported by grants from Simons Foundation and the Tri-Institutional Stem Cell Initiative by the Starr Foundation (Tri-SCI). The authors would like to thank the Mazzoni lab members, Claude Desplan, Danny Reinberg, and Ana Pombo, for feedback and constructive comments; the NYU Genomics Core facility for technical support and data processing; Disi An for establishing the H2B::GFP reporter line; Silvia Velasco for generating input control for ChIP-seq in ESCs; Roland Schwarz for helpful input on the linear models; Albert Tan for quantifying competition experiments; and BioRender.com for creation of graphical abstract and Figure 7 C. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = mar,
day = "15",
doi = "10.1016/j.celrep.2022.110524",
language = "English (US)",
volume = "38",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",
}