TY - JOUR
T1 - CTCF chromatin residence time controls three-dimensional genome organization, gene expression and DNA methylation in pluripotent cells
AU - Soochit, Widia
AU - Sleutels, Frank
AU - Stik, Gregoire
AU - Bartkuhn, Marek
AU - Basu, Sreya
AU - Hernandez, Silvia C.
AU - Merzouk, Sarra
AU - Vidal, Enrique
AU - Boers, Ruben
AU - Boers, Joachim
AU - van der Reijden, Michael
AU - Geverts, Bart
AU - van Cappellen, Wiggert A.
AU - van den Hout, Mirjam
AU - Ozgur, Zeliha
AU - van IJcken, Wilfred F.J.
AU - Gribnau, Joost
AU - Renkawitz, Rainer
AU - Graf, Thomas
AU - Houtsmuller, Adriaan
AU - Grosveld, Frank
AU - Stadhouders, Ralph
AU - Galjart, Niels
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85111652798
UR - https://www.scopus.com/pages/publications/85111652798#tab=citedBy
U2 - 10.1038/s41556-021-00722-w
DO - 10.1038/s41556-021-00722-w
M3 - Article
C2 - 34326481
AN - SCOPUS:85111652798
SN - 1465-7392
VL - 23
SP - 881
EP - 893
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 8
ER -