DNA-Binding Specificities of Human Transcription Factors

详细信息    查看全文

• 作者：Arttu Jolma¹ ; ² ; ⁸ ; Jian Yan¹ ; ⁸ ; Thomas Whitington¹ ; Jarkko Toivonen³ ; Kazuhiro R. Nitta¹ ; Pasi Rastas³ ; Ekaterina Morgunova¹ ; Martin Enge¹ ; Mikko Taipale² ; Gonghong Wei² ; Kimmo Palin² ; Juan M. Vaquerizas⁴ ; Renaud Vincentelli⁵ ; Nicholas M. Luscombe⁴ ; Timothy R. Hughes⁶ ; Patrick Lemaire⁷ ; Esko Ukkonen³ ; Teemu Kivioja¹ ; ² ; ³ ; Jussi Taipale¹ ; ² ; ^{jussi.taipale@ki.se}
• 刊名：Cell
• 出版年：2013
• 出版时间：17 January, 2013
• 年：2013
• 卷：152
• 期：1-2
• 页码：327-339
• 全文大小：2439 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

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.