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Raveh-Sadka T, et al.  (2009) Incorporating nucleosomes into thermodynamic models of transcription regulation. Genome Res 19(8):1480-96

Abstract: Transcriptional control is central to many cellular processes, and, consequently, much effort has been devoted to understanding its underlying mechanisms. The organization of nucleosomes along promoter regions is important for this process, since most transcription factors cannot bind nucleosomal sequences and thus compete with nucleosomes for DNA access. This competition is governed by the relative concentrations of nucleosomes and transcription factors and by their respective sequence binding preferences. However, despite its importance, a mechanistic understanding of the quantitative effects that the competition between nucleosomes and factors has on transcription is still missing. Here we use a thermodynamic framework based on fundamental principles of statistical mechanics to explore theoretically the effect that different nucleosome organizations along promoters have on the activation dynamics of promoters in response to varying concentrations of the regulating factors. We show that even simple landscapes of nucleosome organization reproduce experimental results regarding the effect of nucleosomes as general repressors and as generators of obligate binding cooperativity between factors. Our modeling framework also allows us to characterize the effects that various sequence elements of promoters have on the induction threshold and on the shape of the promoter activation curves. Finally, we show that using only sequence preferences for nucleosomes and transcription factors, our model can also predict expression behavior of real promoter sequences, thereby underscoring the importance of the interplay between nucleosomes and factors in determining expression kinetics.

Status: Published Type: Journal Article | Research Support, Non-U.S. Gov't PubMed ID: 19451592

Topics addressed in this paper

Number of different genes curated to this paper: 12

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GCN4 HHF1 HHF2 HHT1 HHT2 HIS3 HTA1 HTA2 HTB1 HTB2
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Computational analysis blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
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PHO4 PHO5
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