| Literature DB >> 34326481 |
Widia Soochit1, Frank Sleutels1, Gregoire Stik2, Frank Grosveld3, Ralph Stadhouders4,5, Niels Galjart6, Marek Bartkuhn7, Sreya Basu1, Silvia C Hernandez1, Sarra Merzouk8, Enrique Vidal2, Ruben Boers8, Joachim Boers8, Michael van der Reijden1, Bart Geverts9, Wiggert A van Cappellen9, Mirjam van den Hout1,10, Zeliha Ozgur1,10, Wilfred F J van IJcken1,10, Joost Gribnau8, Rainer Renkawitz7, Thomas Graf2, Adriaan Houtsmuller9.
Abstract
The 11 zinc finger (ZF) protein CTCF regulates topologically associating domain formation and transcription through selective binding to thousands of genomic sites. Here, we replaced endogenous CTCF in mouse embryonic stem cells with green-fluorescent-protein-tagged wild-type or mutant proteins lacking individual ZFs to identify additional determinants of CTCF positioning and function. While ZF1 and ZF8-ZF11 are not essential for cell survival, ZF8 deletion strikingly increases the DNA binding off-rate of mutant CTCF, resulting in reduced CTCF chromatin residence time. Loss of ZF8 results in widespread weakening of topologically associating domains, aberrant gene expression and increased genome-wide DNA methylation. Thus, important chromatin-templated processes rely on accurate CTCF chromatin residence time, which we propose depends on local sequence and chromatin context as well as global CTCF protein concentration.Entities:
Year: 2021 PMID： 34326481 DOI： 10.1038/s41556-021-00722-w
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824