The role of response elements organization in transcription factor selectivity: the IFN-β enhanceosome example.

What is the mechanism through which transcription factors (TFs) assemble specifically along the enhancer DNA? The IFN-β enhanceosome provides a good model system: it is small; its components' crystal structures are available; and there are biochemical and cellular data. In the IFN-β enhanceosom...

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Autores principales:	Yongping Pan, Ruth Nussinov
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/95d76da77b504d7cbae0c9da211536a4
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spelling	oai:doaj.org-article:95d76da77b504d7cbae0c9da211536a42021-11-18T05:50:29ZThe role of response elements organization in transcription factor selectivity: the IFN-β enhanceosome example.1553-734X1553-735810.1371/journal.pcbi.1002077https://doaj.org/article/95d76da77b504d7cbae0c9da211536a42011-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21698143/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358What is the mechanism through which transcription factors (TFs) assemble specifically along the enhancer DNA? The IFN-β enhanceosome provides a good model system: it is small; its components' crystal structures are available; and there are biochemical and cellular data. In the IFN-β 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.Yongping PanRuth NussinovPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 6, p e1002077 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Yongping Pan Ruth Nussinov The role of response elements organization in transcription factor selectivity: the IFN-β enhanceosome example.
description	What is the mechanism through which transcription factors (TFs) assemble specifically along the enhancer DNA? The IFN-β enhanceosome provides a good model system: it is small; its components' crystal structures are available; and there are biochemical and cellular data. In the IFN-β 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.
format	article
author	Yongping Pan Ruth Nussinov
author_facet	Yongping Pan Ruth Nussinov
author_sort	Yongping Pan
title	The role of response elements organization in transcription factor selectivity: the IFN-β enhanceosome example.
title_short	The role of response elements organization in transcription factor selectivity: the IFN-β enhanceosome example.
title_full	The role of response elements organization in transcription factor selectivity: the IFN-β enhanceosome example.
title_fullStr	The role of response elements organization in transcription factor selectivity: the IFN-β enhanceosome example.
title_full_unstemmed	The role of response elements organization in transcription factor selectivity: the IFN-β enhanceosome example.
title_sort	role of response elements organization in transcription factor selectivity: the ifn-β enhanceosome example.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/95d76da77b504d7cbae0c9da211536a4
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The role of response elements organization in transcription factor selectivity: the IFN-β enhanceosome example.

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