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Epigenetics and Chromatin

, 8:48

First Online: 24 November 2015Received: 13 August 2015Accepted: 09 November 2015

Abstract

BackgroundCREB-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.

ResultsHere, 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.

ConclusionsWe 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.

KeywordsCBP-p300 Drosophila melanogaster Chromatin structure Gene regulation Insulators Polycomb response elements AbbreviationsCBPCREB-binding protein

ChIP-seqchromatin immunoprecipitation sequencing

CP190centrosomal protein 190kD

dRingsex combs extra

dSfmbtscm-related gene containing four mbt domains

Ezenhancer of zeste

GAFtranscription factor GAGA

H3K4me1monomethylated histone H3 lysine 4

H3K18acacetylated histone H3 lysine 18

H3K23acacetylated histone H3 lysine 23

H3K27acacetylated histone H3 lysine 27

H3K27me3trimethylated histone H3 lysine 27

H3K56acacetylated histone H3 lysine 56

HAThistone acetyltransferase

HCAhierarchical clustering

Mcm2minichromosome maintenance 2

MLLmixed lineage leukemia

NF-kBnuclear factor kappa B

NURF301enhancer of bithorax

Orc2origin recognition complex subunit 2

Pcpolycomb

PCAprincipal component analysis

PCLpolycomb-like

Phopleiohomeotic

PREpolycomb response element

Pscposterior sex combs

RPD3histone deacetylase 1

SMC1structural maintenance of chromosomes 1

STARR-seqself-transcribing active regulatory region sequencing

Su-Hwsuppressor of Hairy wing

Suvar3–7suppressor of variegation 3–7

Trxtrithorax

Electronic supplementary materialThe online version of this article doi:10.1186-s13072-015-0042-4 contains supplementary material, which is available to authorized users.

An erratum to this article can be found at http:-dx.doi.org-10.1186-s13072-016-0088-y.

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Autor: Philge Philip - Ann Boija - Roshan Vaid - Allison M. Churcher - David J. Meyers - Philip A. Cole - Mattias Mannervik - P

Fuente: https://link.springer.com/



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