title: The BET protein FSH functionally interacts with ASH1 to orchestrate global gene activity in Drosophila.
abstract: BACKGROUND
  The question of how cells re-establish gene expression states after cell division is still poorly understood. Genetic and molecular analyses have indicated that Trithorax group (TrxG) proteins are critical for the long-term maintenance of active gene expression states in many organisms. A generally accepted model suggests that TrxG proteins contribute to maintenance of transcription by protecting genes from inappropriate Polycomb group (PcG)-mediated silencing, instead of directly promoting transcription.
  
  
  CONCLUSIONS
  Here we report a physical and functional interaction in Drosophila between two members of the TrxG, the histone methyltransferase ASH1 and the bromodomain and extraterminal family protein FSH. We investigated this interface at the genome level, uncovering a widespread co-localization of both proteins at promoters and PcG-bound intergenic elements. Our integrative analysis of chromatin maps and gene expression profiles revealed that the observed ASH1-FSH binding pattern at promoters is a hallmark of active genes. Inhibition of FSH-binding to chromatin resulted in global down-regulation of transcription. In addition, we found that genes displaying marks of robust PcG-mediated repression also have ASH1 and FSH bound to their promoters.
  
  
  CONCLUSIONS
  Our data strongly favor a global coactivator function of ASH1 and FSH during transcription, as opposed to the notion that TrxG proteins impede inappropriate PcG-mediated silencing, but are dispensable elsewhere. Instead, our results suggest that PcG repression needs to overcome the transcription-promoting function of ASH1 and FSH in order to silence genes.
authors: Tobias
authors: T
authors: Kockmann
authors: Moritz
authors: M
authors: Gerstung
authors: Tommy
authors: T
authors: Schlumpf
authors: Zhu
authors: Z
authors: Xhinzhou
authors: Daniel
authors: D
authors: Hess
authors: Niko
authors: N
authors: Beerenwinkel
authors: Christian
authors: C
authors: Beisel
authors: Renato
authors: R
authors: Paro
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D021901:DNA, Intergenic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: C490910:ASH1 protein, Drosophila; D002843:Chromatin; D021901:DNA, Intergenic; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; C109569:fs(1)h protein, Drosophila