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CBP binding outside of promoters and enhancers in Drosophila melanogaster
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Centre for Cellular and Molecular Biology, Uppal Road, Telangana, India . (Per Stenberg; Computational Life Science Cluster (CLiC))
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). (Per Stenberg)
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2015 (English)In: Epigenetics & Chromatin, ISSN 1756-8935, E-ISSN 1756-8935, Vol. 8, 48Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
BioMed Central, 2015. Vol. 8, 48
Keyword [en]
CBP/p300, Drosophila melanogaster, Chromatin structure, Gene regulation, Insulators, Polycomb response elements
National Category
Bioinformatics and Systems Biology
URN: urn:nbn:se:umu:diva-112435DOI: 10.1186/s13072-015-0042-4ISI: 000365564300001PubMedID: 26604986OAI: diva2:877605
Knut and Alice Wallenberg Foundation, KAW 2014.0018
Available from: 2015-12-07 Created: 2015-12-07 Last updated: 2016-01-04Bibliographically approved

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Philip, PhilgeChurcher, Allison MStenberg, Per
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