Journal article

Authors list: Soochit, W; Sleutels, F; Stik, G; Bartkuhn, M; Basu, S; Hernandez, SC; Merzouk, S; Vidal, E; Boers, R; Boers, J; van der Reijden, M; Geverts, B; van Cappellen, WA; van den Hout, M; Ozgur, Z; van IJcken, WFJ; Gribnau, J; Renkawitz, R; Graf, T; Houtsmuller, A; Grosveld, F; Stadhouders, R; Galjart, N

Publication year: 2021

Pages: 881-893

Journal: Nature Cell Biology

Volume number: 23

Issue number: 8

ISSN: 1465-7392

eISSN: 1476-4679

DOI Link: https://doi.org/10.1038/s41556-021-00722-w

Publisher: Nature Research

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.

Harvard Citation style: Soochit, W., Sleutels, F., Stik, G., Bartkuhn, M., Basu, S., Hernandez, S., et al. (2021) CTCF chromatin residence time controls three-dimensional genome organization, gene expression and DNA methylation in pluripotent cells, Nature Cell Biology, 23(8), pp. 881-893. https://doi.org/10.1038/s41556-021-00722-w

APA Citation style: Soochit, W., Sleutels, F., Stik, G., Bartkuhn, M., Basu, S., Hernandez, S., Merzouk, S., Vidal, E., Boers, R., Boers, J., van der Reijden, M., Geverts, B., van Cappellen, W., van den Hout, M., Ozgur, Z., van IJcken, W., Gribnau, J., Renkawitz, R., Graf, T., ...Galjart, N. (2021). CTCF chromatin residence time controls three-dimensional genome organization, gene expression and DNA methylation in pluripotent cells. Nature Cell Biology. 23(8), 881-893. https://doi.org/10.1038/s41556-021-00722-w