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

Andrew D. Smith, Pavel Sumazin, Zhenyu Xuan, Michael Q. Zhang

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6275-6280
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number16
DOIs
StatePublished - Apr 18 2006

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Keywords

  • Transcription factor binding
  • cis-regulatory modules

ASJC Scopus subject areas

  • General

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