Tissue-specific regulatory elements in mammalian promoters.
Transcription factor-binding sites and the cis-regulatory modules they compose are central determinants of gene expression. We previously showed that binding site motifs and modules in proximal promoters can be used to predict a significant portion of mammalian tissue-specific transcription. Here, we report on a systematic analysis of promoters controlling tissue-specific expression in heart, kidney, liver, pancreas, skeletal muscle, testis and CD4 T cells, for both human and mouse. We integrated multiple sources of expression data to compile sets of transcripts with strong evidence for tissue-specific regulation. The analysis of the promoters corresponding to these sets produced a catalog of predicted tissue-specific motifs and modules, and cis-regulatory elements. Predicted regulatory interactions are supported by statistical evidence, and provide a foundation for targeted experiments that will improve our understanding of tissue-specific regulatory networks. In a broader context, methods used to construct the catalog provide a model for the analysis of genomic regions that regulate differentially expressed genes.
Smith
Andrew D
AD
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Sumazin
Pavel
P
Zhang
Michael Q
MQ
D000465:Algorithms; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019295:Computational Biology; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric; D018511:Systems Integration; D013737:Testis / Q000378:metabolism; D014158:Transcription, Genetic
D012333:RNA, Messenger