CTCF chromatin residence time controls three-dimensional genome organization, gene expression and DNA methylation in pluripotent cells
| Autor: | Joachim Boers, Frank Sleutels, Enrique Vidal, Rainer Renkawitz, Frank Grosveld, Ruben Boers, Niels Galjart, Mirjam C G N van den Hout, Silvia C Hernandez, Wiggert A. van Cappellen, Sarra Merzouk, Adriaan B Houtsmuller, Gregoire Stik, Marek Bartkuhn, Michael van der Reijden, Joost Gribnau, Thomas Graf, Zeliha Ozgur, Sreya Basu, Ralph Stadhouders, Widia Soochit, Bart Geverts, Wilfred F. J. van IJcken |
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| Přispěvatelé: | Cell biology, Developmental Biology, Pathology, Pulmonary Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Pluripotent Stem Cells Embryonic stem cells CCCTC-Binding Factor Time Factors Transcription Elongation Genetic Green Fluorescent Proteins Mitosis Context (language use) Biology Article chemistry.chemical_compound Mice Transcription (biology) Gene expression DNA metabolism Animals Chromosome conformation capture-based methods Zinc finger Nuclear organization Genome Mouse Embryonic Stem Cells Cell Biology DNA Methylation Chromatin Cell biology chemistry Gene Expression Regulation CTCF DNA methylation Mutation Female DNA |
| Zdroj: | Dev Cell Nature Cell Biology, 23(8), 881-893. Nature Publishing Group |
| ISSN: | 1465-7392 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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