Cohesin mediates transcriptional insulation by CCCTC-binding factor.

Abstract

Cohesin complexes mediate sister-chromatid cohesion in dividing cells but may also contribute to gene regulation in postmitotic cells. How cohesin regulates gene expression is not known. Here we describe cohesin-binding sites in the human genome and show that most of these are associated with the CCCTC-binding factor (CTCF), a zinc-finger protein required for transcriptional insulation. CTCF is dispensable for cohesin loading onto DNA, but is needed to enrich cohesin at specific binding sites. Cohesin enables CTCF to insulate promoters from distant enhancers and controls transcription at the H19/IGF2 (insulin-like growth factor 2) locus. This role of cohesin seems to be independent of its role in cohesion. We propose that cohesin functions as a transcriptional insulator, and speculate that subtle deficiencies in this function contribute to 'cohesinopathies' such as Cornelia de Lange syndrome.

• Authors: Kerstin S Wendt, Keisuke Yoshida, Takehiko Itoh, Masashige Bando, Birgit Koch, Erika Schirghuber, Shuichi Tsutsumi, Genta Nagae, Ko Ishihara, Tsuyoshi Mishiro, Kazuhide Yahata, Fumio Imamoto, Hiroyuki Aburatani, Mitsuyoshi Nakao, Naoko Imamoto, Kazuhiro Maeshima, Katsuhiko Shirahige, Jan-Michael Peters
• Journal: Nature (Nature) Vol. 451 Issue 7180 Pg. 796-801 (Feb 14 2008) ISSN: 1476-4687 [Electronic] England
• PMID: 18235444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCCTC-Binding Factor
• CTCF protein, human
• Cell Cycle Proteins
• Chromosomal Proteins, Non-Histone
• Ctcf protein, mouse
• DNA-Binding Proteins
• H19 long non-coding RNA
• IGF2 protein, human
• Nuclear Proteins
• RNA, Long Noncoding
• RNA, Untranslated
• Repressor Proteins
• Insulin-Like Growth Factor II
• DNA

Topics

• Alleles
• Animals
• Brain (cytology, metabolism)
• CCCTC-Binding Factor
• Cell Cycle Proteins (metabolism)
• Cell Differentiation
• Chromosomal Proteins, Non-Histone (metabolism)
• Consensus Sequence (genetics)
• DNA (genetics, metabolism)
• DNA-Binding Proteins (metabolism)
• Enhancer Elements, Genetic (genetics)
• Female
• Gene Expression Regulation (genetics)
• Genome, Human (genetics)
• HeLa Cells
• Humans
• Insulin-Like Growth Factor II (genetics)
• Mice
• Mitosis
• Mothers
• Nuclear Proteins (metabolism)
• Promoter Regions, Genetic (genetics)
• RNA, Long Noncoding
• RNA, Untranslated (genetics)
• Repressor Proteins (metabolism)
• Transcription, Genetic (genetics)
• Cohesins