title: Signal transducer and activator of transcription STAT5 is recruited to c-Myc super-enhancer.
abstract: BACKGROUND
  c-Myc has been proposed as a putative target gene of signal transducer and activator of transcription 5 (STAT5). No functional STAT5 binding site has been identified so far within the c-Myc gene locus, therefore a direct transcriptional regulation by STAT5 remains uncertain. c-Myc super-enhancer, located 1.7 Mb downstream of the c-Myc gene locus, was recently reported as essential for the regulation of c-Myc gene expression by hematopoietic transcription factors and bromodomain and extra-terminal (BET) proteins and for leukemia maintenance. c-Myc super-enhancer is composed of five regulatory regions (E1-E5) which recruit transcription and chromatin-associated factors, mediating chromatin looping and interaction with the c-Myc promoter.
  
  
  RESULTS
  We now show that STAT5 strongly binds to c-Myc super-enhancer regions E3 and E4, both in normal and transformed Ba/F3 cells. We also found that the BET protein bromodomain-containing protein 2 (BRD2), a co-factor of STAT5, co-localizes with STAT5 at E3/E4 in Ba/F3 cells transformed by the constitutively active STAT5-1*6 mutant, but not in non-transformed Ba/F3 cells. BRD2 binding at E3/E4 coincides with c-Myc transcriptional activation and is lost upon treatment with deacetylase and BET inhibitors, both of which inhibit STAT5 transcriptional activity and c-Myc gene expression.
  
  
  CONCLUSIONS
  Our data suggest that constitutive STAT5 binding to c-Myc super-enhancer might contribute to BRD2 maintenance and thus allow sustained expression of c-Myc in Ba/F3 cells transformed by STAT5-1*6.
authors.affiliation: Stat5 Signaling Research Group, Institute of Immunology, University of Regensburg, 93053, Regensburg, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Pinz
authors.affiliation: Stat5 Signaling Research Group, Institute of Immunology, University of Regensburg, 93053, Regensburg, Germany.
authors.forename: Samy
authors.initials: S
authors.lastname: Unser
authors.affiliation: Stat5 Signaling Research Group, Institute of Immunology, University of Regensburg, 93053, Regensburg, Germany. anne.rascle@klinik.uni-regensburg.de.
authors.forename: Anne
authors.initials: A
authors.lastname: Rascle
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002461:Cell Line, Transformed; D005786:Gene Expression Regulation; D016259:Genes, myc; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors; D000092468:Bromodomain Containing Proteins
chemical_list: D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D011956:Receptors, Cell Surface; D050799:STAT5 Transcription Factor; D014157:Transcription Factors; C098415:BRD2 protein, human; D000092468:Bromodomain Containing Proteins; C486765:Dner protein, mouse
keywords: BET; BRD2; Chromatin; STAT5; Super-enhancer; c-Myc