DNA-binding specificities of human transcription factors

Cell. 2013 Jan 17;152(1-2):327-39. doi: 10.1016/j.cell.2012.12.009.

Arttu Jolma ¹, Jian Yan, Thomas Whitington, Jarkko Toivonen, Kazuhiro R Nitta, Pasi Rastas, Ekaterina Morgunova, Martin Enge, Mikko Taipale, Gonghong Wei, Kimmo Palin, Juan M Vaquerizas, Renaud Vincentelli, Nicholas M Luscombe, Timothy R Hughes, Patrick Lemaire, Esko Ukkonen, Teemu Kivioja, Jussi Taipale

Affiliations

Affiliation

1 Science for Life Center, Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, Sweden.

PMID: 23332764 DOI: 10.1016/j.cell.2012.12.009

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.

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