CBP binding outside of promoters and enhancers in Drosophila melanogaster

Epigenetics & Chromatin

Per Stenberg⁴  Mattias Mannervik¹  Philip A. Cole⁵  David J. Meyers⁵  Allison M. Churcher²  Roshan Vaid¹  Ann Boija¹  Philge Philip³ 

[1] Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, 106 91, Sweden;Department of Molecular Biology, Umeå University, Umeå, 901 87, Sweden;Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, Telangana, India;Division of CBRN Security and Defence, FOI–Swedish Defence Research Agency, Umeå, Sweden;Department Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore 21205, MD, USA

关键词: Polycomb response elements;    Insulators;    Gene regulation;    Chromatin structure;    Drosophila melanogaster;    CBP/p300;   

Others  :  1234468
DOI  :  10.1186/s13072-015-0042-4

 received in 2015-08-13, accepted in 2015-11-09,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Philip et al.

【 图 表 】

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