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PMID:22780989

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Citation

Faure, AJ, Schmidt, D, Watt, S, Schwalie, PC, Wilson, MD, Xu, H, Ramsay, RG, Odom, DT and Flicek, P (2012) Cohesin regulates tissue-specific expression by stabilizing highly occupied cis-regulatory modules. Genome Res. 22:2163-75

Abstract

The cohesin protein complex contributes to transcriptional regulation in a CTCF-independent manner by colocalizing with master regulators at tissue-specific loci. The regulation of transcription involves the concerted action of multiple transcription factors (TFs) and cohesin's role in this context of combinatorial TF binding remains unexplored. To investigate cohesin-non-CTCF (CNC) binding events in vivo we mapped cohesin and CTCF, as well as a collection of tissue-specific and ubiquitous transcriptional regulators using ChIP-seq in primary mouse liver. We observe a positive correlation between the number of distinct TFs bound and the presence of CNC sites. In contrast to regions of the genome where cohesin and CTCF colocalize, CNC sites coincide with the binding of master regulators and enhancer-markers and are significantly associated with liver-specific expressed genes. We also show that cohesin presence partially explains the commonly observed discrepancy between TF motif score and ChIP signal. Evidence from these statistical analyses in wild-type cells, and comparisons to maps of TF binding in Rad21-cohesin haploinsufficient mouse liver, suggests that cohesin helps to stabilize large protein-DNA complexes. Finally, we observe that the presence of mirrored CTCF binding events at promoters and their nearby cohesin-bound enhancers is associated with elevated expression levels.

Links

PubMed PMC3483546 Online version:10.1101/gr.136507.111

Keywords

Animals; Cell Cycle Proteins/metabolism; Chromatin Immunoprecipitation; Chromosomal Proteins, Non-Histone/metabolism; Gene Regulatory Networks; Genome; Haploinsufficiency; Mice; Mice, Inbred C57BL; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Organ Specificity; Phosphoproteins/genetics; Phosphoproteins/metabolism; Promoter Regions, Genetic; Protein Binding; Repressor Proteins/metabolism; Sequence Analysis, DNA; Transcription Factors/metabolism; Transcription, Genetic; Up-Regulation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:EP300

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:HNF6

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:STAG2

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:PKNX1

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:HNF1A

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:FOXA1

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:FOXA2

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:CBP

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:HNF4A

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:CEBPA

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:GABPA

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:CTCF

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:E2F4

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:REST

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:STAG1

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97501)

Seeded From UniProt

complete

MOUSE:FOXA2

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:CBP

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:EP300

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:CEBPA

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

Notes

See also

References

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