DNA motifs in human and mouse proximal promoters predict tissue-specific expression

Smith, A. D., Sumazin, P., Xuan, Z., Zhang, M. Q. (April 2006) DNA motifs in human and mouse proximal promoters predict tissue-specific expression. Proc Natl Acad Sci U S A, 103 (16). pp. 6275-80. ISSN 0027-8424 (Print)

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URL: https://www.ncbi.nlm.nih.gov/pubmed/16606849
DOI: 10.1073/pnas.0508169103


Comprehensive identification of cis-regulatory elements is necessary for accurately reconstructing gene regulatory networks. We studied proximal promoters of human and mouse genes with differential expression across 56 terminally differentiated tissues. Using in silico techniques to discover, evaluate, and model interactions among sequence elements, we systematically identified regulatory modules that distinguish elevated from inhibited expression in the corresponding transcripts. We used these putative regulatory modules to construct a single predictive model for each of the 56 tissues. These predictors distinguish tissue-specific elevated from inhibited expression with statistical significance in 80% of the tissues (45 of 56). The predictors also reveal synergy between cis-regulatory modules and explain large-scale tissue-specific differential expression. For testis and liver, the predictors include computationally predicted motifs. For most other tissues, the predictors reveal synergy between experimentally verified motifs and indicate genes that are regulated by similar tissue-specific machinery. The identification in proximal promoters of cis-regulatory modules with tissue-specific activity lays the groundwork for complete characterization and deciphering of cis-regulatory DNA code in mammalian genomes.

Item Type: Paper
Uncontrolled Keywords: Animals Cell Cycle genetics physiology Computational Biology Gene Expression Humans Liver metabolism Mice Promoter Regions genetics T-Lymphocytes metabolism Tissue Distribution
Subjects: bioinformatics > computational biology
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA expression > promoter
CSHL Authors:
Communities: CSHL labs > Zhang lab
Depositing User: CSHL Librarian
Date: 18 April 2006
Date Deposited: 09 Dec 2011 16:27
Last Modified: 09 Nov 2017 16:15
PMCID: PMC1458868
Related URLs:
URI: https://repository.cshl.edu/id/eprint/22901

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