PT  - JOURNAL ARTICLE
AU  - Gordana Wutz
AU  - Csilla Várnai
AU  - Kota Nagasaka
AU  - David A Cisneros
AU  - Roman Stocsits
AU  - Wen Tang
AU  - Stefan Schoenfelder
AU  - Gregor Jessberger
AU  - Matthias Muhar
AU  - M Julius Hossain
AU  - Nike Walther
AU  - Birgit Koch
AU  - Moritz Kueblbeck
AU  - Jan Ellenberg
AU  - Johannes Zuber
AU  - Peter Fraser
AU  - Jan-Michael Peters
TI  - CTCF, WAPL and PDS5 proteins control the formation of TADs and loops by cohesin
AID  - 10.1101/177444
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 177444
4099  - http://biorxiv.org/content/early/2017/08/18/177444.short
4100  - http://biorxiv.org/content/early/2017/08/18/177444.full
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.