RT Journal Article
SR Electronic
T1 CTCF, WAPL and PDS5 proteins control the formation of TADs and loops by cohesin
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 177444
DO 10.1101/177444
A1 Gordana Wutz
A1 Csilla Várnai
A1 Kota Nagasaka
A1 David A Cisneros
A1 Roman Stocsits
A1 Wen Tang
A1 Stefan Schoenfelder
A1 Gregor Jessberger
A1 Matthias Muhar
A1 M Julius Hossain
A1 Nike Walther
A1 Birgit Koch
A1 Moritz Kueblbeck
A1 Jan Ellenberg
A1 Johannes Zuber
A1 Peter Fraser
A1 Jan-Michael Peters
YR 2017
UL http://biorxiv.org/content/early/2017/08/18/177444.abstract
AB Mammalian genomes are organized into compartments, topologically-associating domains (TADs) and loops to facilitate gene regulation and other chromosomal functions. Compartments are formed by nucleosomal interactions, but how TADs and loops are generated is unknown. It has been proposed that cohesin forms these structures by extruding loops until it encounters CTCF, but direct evidence for this hypothesis is missing. Here we show that cohesin suppresses compartments but is essential for TADs and loops, that CTCF defines their boundaries, and that WAPL and its PDS5 binding partners control the length of chromatin loops. In the absence of WAPL and PDS5 proteins, cohesin passes CTCF sites with increased frequency, forms extended chromatin loops, accumulates in axial chromosomal positions (vermicelli) and condenses chromosomes to an extent normally only seen in mitosis. These results show that cohesin has an essential genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA by WAPL.