Distinct isoforms of the Drosophila Brd4 homologue are present at enhancers, promoters and insulator sites.
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.
Department of Biology, Emory University, Atlanta, GA 30322, USA and Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA 30322, USA.
Wendy A
WA
Kellner
Kevin
K
Van Bortle
Li
L
Li
Edward
E
Ramos
Naomi
N
Takenaka
Victor G
VG
Corces
D000818:Animals; D002460:Cell Line; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics; D004742:Enhancer Elements, Genetic; D006657:Histones / Q000378:metabolism; D038101:Insulator Elements; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D006657:Histones; D020033:Protein Isoforms; D014157:Transcription Factors; C109569:fs(1)h protein, Drosophila