title: Coregulation of transcription factor binding and nucleosome occupancy through DNA features of mammalian enhancers.
abstract: Transcription factors (TFs) preferentially bind sites contained in regions of computationally predicted high nucleosomal occupancy, suggesting that nucleosomes are gatekeepers of TF binding sites. However, because of their complexity mammalian genomes contain millions of randomly occurring, unbound TF consensus binding sites. We hypothesized that the information controlling nucleosome assembly may coincide with the information that enables TFs to bind cis-regulatory elements while ignoring randomly occurring sites. Hence, nucleosomes would selectively mask genomic sites that can be contacted by TFs and thus be potentially functional. The hematopoietic pioneer TF Pu.1 maintained nucleosome depletion at macrophage-specific enhancers that displayed a broad range of nucleosome occupancy in other cell types and in reconstituted chromatin. We identified a minimal set of DNA sequence and shape features that accurately predicted both Pu.1 binding and nucleosome occupancy genome-wide. These data reveal a basic organizational principle of mammalian cis-regulatory elements whereby TF recruitment and nucleosome deposition are controlled by overlapping DNA sequence features.
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), Via Adamello 16, I-20139 Milan, Italy.
authors.forename: Iros
authors.initials: I
authors.lastname: Barozzi
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), Via Adamello 16, I-20139 Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Simonatto
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), Via Adamello 16, I-20139 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bonifacio
authors.affiliation: Molecular and Computational Biology Program, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Molecular and Computational Biology Program, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Remo
authors.initials: R
authors.lastname: Rohs
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), Via Adamello 16, I-20139 Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Ghisletti
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), Via Adamello 16, I-20139 Milan, Italy.
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Natoli
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D016384:Consensus Sequence; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017422:Sequence Analysis, DNA; D060388:Support Vector Machine; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D009707:Nucleosomes; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1