• AJ Faure, D Schmidt, S Watt, PC Schwalie, MD Wilson, H Xu, RG Ramsay, DT Odom, P Flicek. Cohesin regulates tissue-specific expression by stabilizing highly occupied cis-regulatory modules. Genome Res 2012;22(11):2163–2175. doi:10.1101/gr.136507.111
  [BibTeX] [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

  @Article{22780989,
  author = {Faure AJ and Schmidt D and Watt S and Schwalie PC and Wilson MD and Xu H and Ramsay RG and Odom DT and Flicek P},
  title = {Cohesin regulates tissue-specific expression by stabilizing highly occupied cis-regulatory modules},
  journal = {Genome Res},
  volume = {22},
  number = {11},
  pages = {2163--2175},
  year = {2012},
  doi = {10.1101/gr.136507.111},
  howpublished = {Advanced online publication: 10 July 2012},
  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},}

Description

As published in  Genome Research .

Raw Data

All ChIP-seq reads can be found in ArrayExpress with accession number E-MTAB-941

Peak calls

ChIP-seq peak calls made using SWEMBL are provided in both SWEMBL output and bed file format (chr, start, end) for the mouse embryonic stem cell and mouse liver cell  data.

Aligned reads

Aligned reads in bed file format for all data sets generated for this project can be downloaded  here . Bed files with and without identical duplicate reads are available.

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