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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Enhancer Elements, Genetic*
  • Histones / metabolism
  • Insulator Elements*
  • Promoter Regions, Genetic*
  • Protein Isoforms / metabolism
  • Transcription Factors / metabolism*
  • Transcription, Genetic

Substances

  • Drosophila Proteins
  • Histones
  • Protein Isoforms
  • Transcription Factors
  • fs(1)h protein, Drosophila

Associated data

  • GEO/GSE42086