title: Inducible super-enhancers are organized based on canonical signal-specific transcription factor binding elements.
abstract: Super-enhancers are established through the interactions of several enhancers and a large number of proteins, including transcription factors and co-regulators; however, the formation of these interactions is poorly understood. By re-analysing previously published estrogen receptor alpha (ERα) ChIP-seq data sets derived from the MCF-7 cell line, we observed that in the absence of stimulation, future super-enhancers are represented by one or a few transcription factor binding event(s) and these extraordinary enhancers possess a response element largely specific to the ERα dimer. Upon hormonal stimulation, these primary binding sites are surrounded by a large amount of ERα and the critical components of active enhancers, such as P300 and MED1, and together with neighbouring sites bound by newly recruited ERα, they generate the functional super-enhancers. To further validate the role of canonical elements in super-enhancer formation, we investigated some additional signal-dependent transcription factors, confirming that certain, distinguished binding elements have a general organizer function. These results suggest that certain signal-specific transcription factors guide super-enhancer formation upon binding to strong response elements. These findings may reshape the current understanding of how these regulatory units assemble, highlighting the involvement of DNA elements instead of protein-protein interactions.
authors.affiliation: Department of Biochemistry and Molecular Biology, Genomic Medicine and Bioinformatic Core Facility, University of Debrecen, Debrecen 4032, Hungary.
authors.forename: Dóra
authors.initials: D
authors.lastname: Bojcsuk
authors.affiliation: Department of Biochemistry and Molecular Biology, MTA-DE 'Lendulet' Immunogenomics Research Group, University of Debrecen, Debrecen 4032, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Nagy
authors.affiliation: Department of Biochemistry and Molecular Biology, Genomic Medicine and Bioinformatic Core Facility, University of Debrecen, Debrecen 4032, Hungary.
authors.forename: Balint L
authors.initials: BL
authors.lastname: Balint
mesh_terms: D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D047628:Estrogen Receptor alpha / Q000378:metabolism; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D015398:Signal Transduction; D050656:Transcription Factor AP-2 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D050656:Transcription Factor AP-2; D014157:Transcription Factors