title: DNA-binding specificities of human transcription factors.
abstract: Although the proteins that read the gene regulatory code, transcription factors (TFs), have been largely identified, it is not well known which sequences TFs can recognize. We have analyzed the sequence-specific binding of human TFs using high-throughput SELEX and ChIP sequencing. A total of 830 binding profiles were obtained, describing 239 distinctly different binding specificities. The models represent the majority of human TFs, approximately doubling the coverage compared to existing systematic studies. Our results reveal additional specificity determinants for a large number of factors for which a partial specificity was known, including a commonly observed A- or T-rich stretch that flanks the core motifs. Global analysis of the data revealed that homodimer orientation and spacing preferences, and base-stacking interactions, have a larger role in TF-DNA binding than previously appreciated. We further describe a binding model incorporating these features that is required to understand binding of TFs to DNA.
authors: Science for Life Center, Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, Sweden.
authors: Arttu
authors: A
authors: Jolma
authors: Jian
authors: J
authors: Yan
authors: Thomas
authors: T
authors: Whitington
authors: Jarkko
authors: J
authors: Toivonen
authors: Kazuhiro R
authors: KR
authors: Nitta
authors: Pasi
authors: P
authors: Rastas
authors: Ekaterina
authors: E
authors: Morgunova
authors: Martin
authors: M
authors: Enge
authors: Mikko
authors: M
authors: Taipale
authors: Gonghong
authors: G
authors: Wei
authors: Kimmo
authors: K
authors: Palin
authors: Juan M
authors: JM
authors: Vaquerizas
authors: Renaud
authors: R
authors: Vincentelli
authors: Nicholas M
authors: NM
authors: Luscombe
authors: Timothy R
authors: TR
authors: Hughes
authors: Patrick
authors: P
authors: Lemaire
authors: Esko
authors: E
authors: Ukkonen
authors: Teemu
authors: T
authors: Kivioja
authors: Jussi
authors: J
authors: Taipale
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000737:chemistry; D006801:Humans; D008390:Markov Chains; D051379:Mice; D008954:Models, Biological; D010802:Phylogeny; D052156:SELEX Aptamer Technique; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D004247:DNA