title: High constitutive activity of a broad panel of housekeeping and tissue-specificcis-regulatory elements depends on a subset of ETS proteins.
abstract: Enhancers and promoters that control the transcriptional output of terminally differentiated cells include cell type-specific and broadly active housekeeping elements. Whether the high constitutive activity of these two groups ofcis-regulatory elements relies on entirely distinct or instead also on shared regulators is unknown. By dissecting thecis-regulatory repertoire of macrophages, we found that the ELF subfamily of ETS proteins selectively bound within 60 base pairs (bp) from the transcription start sites of highly active housekeeping genes. ELFs also bound constitutively active, but not poised, macrophage-specific enhancers and promoters. The role of ELFs in promoting high-level constitutive transcription was suggested by multiple evidence: ELF sites enabled robust transcriptional activation by endogenous and minimal synthetic promoters, ELF recruitment was stabilized by the transcriptional machinery, and ELF proteins mediated recruitment of transcriptional and chromatin regulators to core promoters. These data suggest that the co-optation of a limited number of highly active transcription factors represents a broadly adopted strategy to equip both cell type-specific and housekeepingcis-regulatory elements with the ability to efficiently promote transcription.
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Curina
authors.affiliation: Humanitas Clinical and Research Center, 20089 Rozzano-Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Termanini
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy.
authors.forename: Iros
authors.initials: I
authors.lastname: Barozzi
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Prosperini
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Simonatto
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Polletti
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Silvola
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Soldi
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy.
authors.forename: Liv
authors.initials: L
authors.lastname: Austenaa
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bonaldi
authors.affiliation: Humanitas Clinical and Research Center, 20089 Rozzano-Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Ghisletti
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy.|Humanitas University, 20089 Rozzano-Milan, Italy.
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Natoli
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D020043:Genes, Essential / Q000235:genetics*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D021381:Protein Transport; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D014157:Transcription Factors
keywords: ETS; enhancers; housekeeping genes; macrophages; transcription