Mechanisms of transcription factor selectivity

Yongping Pan*, Chung Jung Tsai, Buyong Ma, Ruth Nussinov

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


The initiation of transcription is regulated by transcription factors (TFs) binding to DNA response elements (REs). How do TFs recognize specific binding sites among the many similar ones available in the genome? Recent research has illustrated that even a single nucleotide substitution can alter the selective binding of TFs to coregulators, that prior binding events can lead to selective DNA binding, and that selectivity is influenced by the availability of binding sites in the genome. Here, we combine structural insights with recent genomics screens to address the problem of TF-DNA interaction specificity. The emerging picture of selective binding site sequence recognition and TF activation involves three major factors: the cellular network, protein and DNA as dynamic conformational ensembles and the tight packing of multiple TFs and coregulators on stretches of regulatory DNA. The classification of TF recognition mechanisms based on these factors impacts our understanding of how transcription initiation is regulated.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalTrends in Genetics
Issue number2
StatePublished - Feb 2010


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