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

• Type of Material: Article
• Authors: Wendy A. Kellner, Emory University; Kevin Van Bortle, Emory University; Li Li, Emory University; Edward Ramos, Emory University; Naomi Takenaka, Emory University; Victor Corces, Emory University
• Language: English
• Date: 2013-11
• Publisher: Oxford University Press (OUP)
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2013. Published by Oxford University Press.
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://nar.oxfordjournals.org/content/41/20/9274
• Title of Journal or Parent Work: Nucleic Acids Research
• ISSN: 0305-1048
• Volume: 41
• Issue: 20
• Start Page: 9274
• End Page: 9283
• Grant/Funding Information: Funding for open access charge: NIH [R01GM035463].; National Institute of General Medical Sciences of the National Institutes of Health under award [R01GM035463].
• Research Categories: Biology, Molecular; Biology, Cell

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.