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Nucleic Acids Res. 2013 Nov;41(20):9274-83. doi: 10.1093/nar/gkt722. Epub 2013 Aug 13.

Distinct isoforms of the Drosophila Brd4 homologue are present at enhancers, promoters and insulator sites.

Author information

1
Department of Biology, Emory University, Atlanta, GA 30322, USA and Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA 30322, USA.

Abstract

Brd4 is a double bromodomain protein that has been shown to interact with acetylated histones to regulate transcription by recruiting Positive Transcription Elongation Factor b to the promoter region. Brd4 is also involved in gene bookmarking during mitosis and is a therapeutic target for the treatment of acute myeloid leukemia. The Drosophila melanogaster Brd4 homologue is called Fs(1)h and, like its vertebrate counterpart, encodes different isoforms. We have used ChIP-seq to examine the genome-wide distribution of Fs(1)h isoforms. We are able to distinguish the Fs(1)h-L and Fs(1)h-S binding profiles and discriminate between the genomic locations of the two isoforms. Fs(1)h-S is present at enhancers and promoters and its amount parallels transcription levels. Correlations between the distribution of Fs(1)h-S and various forms of acetylated histones H3 and H4 suggest a preference for binding to H3K9acS10ph. Surprisingly, Fs(1)h-L is located at sites in the genome where multiple insulator proteins are also present. The results suggest that Fs(1)h-S may be responsible for the classical role assigned to this protein, whereas Fs(1)h-L may have a new and unexpected role in chromatin architecture by working in conjunction with insulator proteins to mediate intra- or inter-chromosome interactions.

PMID:
23945939
PMCID:
PMC3814382
DOI:
10.1093/nar/gkt722
[Indexed for MEDLINE]
Free PMC Article

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