title: CBP binding outside of promoters and enhancers in Drosophila melanogaster.
abstract: BACKGROUND
  CREB-binding protein (CBP, also known as nejire) is a transcriptional co-activator that is conserved in metazoans. CBP plays an important role in embryonic development and cell differentiation and mutations in CBP can lead to various diseases in humans. In addition, CBP and the related p300 protein have successfully been used to predict enhancers in both humans and flies when they occur with monomethylation of histone H3 on lysine 4 (H3K4me1).
  
  
  RESULTS
  Here, we compare CBP chromatin immunoprecipitation sequencing data from Drosophila S2 cells with modENCODE data and show that CBP is bound at genomic sites with a wide range of functions. As expected, we find that CBP is bound at active promoters and enhancers. In addition, we find that the strongest CBP sites in the genome are found at Polycomb response elements embedded in histone H3 lysine 27 trimethylated (H3K27me3) chromatin, where they correlate with binding of the Pho repressive complex. Interestingly, we find that CBP also binds to most insulators in the genome. At a subset of these, CBP may regulate insulating activity, measured as the ability to prevent repressive H3K27 methylation from spreading into adjacent chromatin.
  
  
  CONCLUSIONS
  We conclude that CBP could be involved in a much wider range of functions than has previously been appreciated, including Polycomb repression and insulator activity. In addition, we discuss the possibility that a common role for CBP at all functional elements may be to regulate interactions between distant chromosomal regions and speculate that CBP is controlling higher order chromatin organization.
authors.affiliation: Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden ; Computational Life Science Cluster (CLiC), Umeå University, 901 87 Umeå, Sweden ; Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, Telangana 500007 India.
authors.forename: Philge
authors.initials: P
authors.lastname: Philip
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Ann
authors.initials: A
authors.lastname: Boija
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Roshan
authors.initials: R
authors.lastname: Vaid
authors.affiliation: Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Churcher
authors.affiliation: Department Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Meyers
authors.affiliation: Department Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Cole
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Mannervik
authors.affiliation: Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden ; Computational Life Science Cluster (CLiC), Umeå University, 901 87 Umeå, Sweden ; Division of CBRN Security and Defence, FOI-Swedish Defence Research Agency, Umeå, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Stenberg
keywords: CBP/p300; Chromatin structure; Drosophila melanogaster; Gene regulation; Insulators; Polycomb response elements