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Determining Physical Constraints in Transcriptional Initiation Complexes Using DNA Sequence Analysis

Journal Article · · PLoS ONE
 [1];  [2];  [3];  [4]
  1. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; DOE/OSTI
  2. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology
  3. Univ. of California, Berkeley, CA (United States). Graduate Group in Biophysics
  4. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division. Dept. of Genome Sciences
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Eukaryotic gene expression is often under the control of cooperatively acting transcription factors whose binding is limited by structural constraints. By determining these structural constraints, we can understand the ‘‘rules’’ that define functional cooperativity. Conversely, by understanding the rules of binding, we can infer structural characteristics. We have developed an information theory based method for approximating the physical limitations of cooperative interactions by comparing sequence analysis to microarray expression data. When applied to the coordinated binding of the sulfur amino acid regulatory protein Met4 by Cbf1 and Met31, we were able to create a combinatorial model that can correctly identify Met4 regulated genes. Interestingly, we found that the major determinant of Met4 regulation was the sum of the strength of the Cbf1 and Met31 binding sites and that the energetic costs associated with spacing appeared to be minimal.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1627339
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 11 Vol. 2; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (2)

Dissection of Combinatorial Control by the Met4 Transcriptional Complex journal February 2010
Probing the Informational and Regulatory Plasticity of a Transcription Factor DNA–Binding Domain journal March 2012

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