A CTCF-independent Role for Cohesin in Tissue-specific Transcription

Overview

Journal Genome Res

Specialty Genetics

Date 2010 Mar 12

PMID 20219941

Citations 234

Authors

Dominic Schmidt

Petra C Schwalie

Caryn S Ross-Innes

Antoni Hurtado

Gordon D Brown

Jason S Carroll

Paul Flicek

Duncan T Odom

Affiliations

Soon will be listed here.

Abstract

The cohesin protein complex holds sister chromatids in dividing cells together and is essential for chromosome segregation. Recently, cohesin has been implicated in mediating transcriptional insulation, via its interactions with CTCF. Here, we show in different cell types that cohesin functionally behaves as a tissue-specific transcriptional regulator, independent of CTCF binding. By performing matched genome-wide binding assays (ChIP-seq) in human breast cancer cells (MCF-7), we discovered thousands of genomic sites that share cohesin and estrogen receptor alpha (ER) yet lack CTCF binding. By use of human hepatocellular carcinoma cells (HepG2), we found that liver-specific transcription factors colocalize with cohesin independently of CTCF at liver-specific targets that are distinct from those found in breast cancer cells. Furthermore, estrogen-regulated genes are preferentially bound by both ER and cohesin, and functionally, the silencing of cohesin caused aberrant re-entry of breast cancer cells into cell cycle after hormone treatment. We combined chromosomal interaction data in MCF-7 cells with our cohesin binding data to show that cohesin is highly enriched at ER-bound regions that capture inter-chromosomal loop anchors. Together, our data show that cohesin cobinds across the genome with transcription factors independently of CTCF, plays a functional role in estrogen-regulated transcription, and may help to mediate tissue-specific transcriptional responses via long-range chromosomal interactions.

Citing Articles

Cohesin positions the epigenetic reader Phf2 within the genome.

Tang W, Costantino L, Stocsits R, Wutz G, Ladurner R, Hudecz O EMBO J. 2025; 44(3):736-766.

PMID: 39748119 PMC: 11790891. DOI: 10.1038/s44318-024-00348-2.

Transcription factors form a ternary complex with NIPBL/MAU2 to localize cohesin at enhancers.

Fettweis G, Wagh K, Stavreva D, Jimenez-Panizo A, Kim S, Lion M bioRxiv. 2024; .

PMID: 39713324 PMC: 11661173. DOI: 10.1101/2024.12.09.627537.

Emerging roles of cohesin-STAG2 in cancer.

Scott J, Al Ayadi L, Epeslidou E, van Scheppingen R, Mukha A, Kaaij L Oncogene. 2024; 44(5):277-287.

PMID: 39613934 DOI: 10.1038/s41388-024-03221-y.

Cohesin composition and dosage independently affect early development in zebrafish.

Labudina A, Meier M, Gimenez G, Tatarakis D, Ketharnathan S, Mackie B Development. 2024; 151(15).

PMID: 38975838 PMC: 11317101. DOI: 10.1242/dev.202593.

Machine learning enables pan-cancer identification of mutational hotspots at persistent CTCF binding sites.

Chen W, Zeng Y, Achinger-Kawecka J, Campbell E, Jones A, Stewart A Nucleic Acids Res. 2024; 52(14):8086-8099.

PMID: 38950902 PMC: 11317138. DOI: 10.1093/nar/gkae530.

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