The role of response elements organization in transcription factor selectivity: The ifn-β enhanceosome example

Yongping Pan, Ruth Nussinov

Research output: Contribution to journalArticlepeer-review

Abstract

What is the mechanism through which transcription factors (TFs) assemble specifically along the enhancer DNA? The IFN-benhanceosome provides a good model system: it is small; its components' crystal structures are available; and there are biochemical and cellular data. In the IFN-b enhanceosome, there are few protein-protein interactions even though consecutive DNA response elements (REs) overlap. Our molecular dynamics (MD) simulations on different motif combinations from the enhanceosome illustrate that cooperativity is achieved via unique organization of the REs: specific binding of one TF can enhance the binding of another TF to a neighboring RE and restrict others, through overlap of REs; the order of the REs can determine which complexes will form; and the alternation of consensus and non-consensus REs can regulate binding specificity by optimizing the interactions among partners. Our observations offer an explanation of how specificity and cooperativity can be attained despite the limited interactions between neighboring TFs on the enhancer DNA. To date, when addressing selective TF binding, attention has largely focused on RE sequences. Yet, the order of the REs on the DNA and the length of the spacers between them can be a key factor in specific combinatorial assembly of the TFs on the enhancer and thus in function. Our results emphasize cooperativity via RE binding sites organization.

Original languageEnglish
Article numbere1002077
JournalPLoS Computational Biology
Volume7
Issue number6
DOIs
StatePublished - Jun 2011

Fingerprint

Dive into the research topics of 'The role of response elements organization in transcription factor selectivity: The ifn-β enhanceosome example'. Together they form a unique fingerprint.

Cite this