Data/hora: 13/06/2024 11:04:02

Provedor de dados: 	17	
País: 	United Kingdom	
Título: 	Nucleosome-mediated cooperativity between transcription factors	
Autores: 	Leonid A. Mirny.	
Data: 	2009-01-16	
Ano: 	2009	
Palavras-chave: 	Developmental Biology; Genetics &amp; Genomics; Molecular Cell Biology; Bioinformatics.	
Resumo: 	Cooperative binding of transcription factors (TFs) to cis-regulatory regions (CRRs) is essential for precision of gene expression in development and other processes. The classical model of cooperativity requires direct interactions between TFs, thus constraining the arrangement of TFs sites in a CRR. On the contrary, genomic and functional studies demonstrate a great deal of flexibility in such arrangements with variable distances, numbers of sites, and identities of the involved TFs. Such flexibility is inconsistent with the cooperativity by direct interactions between TFs. Here we demonstrate that strong cooperativity among non-interacting TFs can be achieved by their competition with nucleosomes. We find that the mechanism of nucleosome-mediated cooperativity is mathematically identical to the Monod-Wyman-Changeux (MWC) model of cooperativity in hemoglobin. This surprising parallel provides deep insights, with parallels between heterotropic regulation of hemoglobin (e.g. Bohr effect) and roles of nucleosome-positioning sequences and chromatin modifications in gene regulation. Characterized mechanism is consistent with numerous experimental results, allows substantial flexibility in and modularity of CRRs, and provides a rationale for a broad range of genomic and evolutionary observations. Striking parallels between cooperativity in hemoglobin and in transcription regulation point at a new design principle that may be used in range of biological systems.	
Tipo: 	Manuscript	
Identificador: 	http://precedings.nature.com/documents/2796/version/1

oai:nature.com:10101/npre.2009.2796.1

http://hdl.handle.net/10101/npre.2009.2796.1	
Fonte: 	Nature Precedings	
Fonte: 	Creative Commons Attribution 3.0 License