comprehensive annotation of bidirectional promoters identifies co-regulation among breast and ovarian cancer genes全面注释之间的双向启动子识别co-regulation乳腺癌和卵巢癌的基因.pdfVIP

Comprehensive Annotation of Bidirectional Promoters Identifies Co-Regulation among Breast and Ovarian Cancer Genes 1 2 1* Mary Q. Yang , Laura M. Koehly , Laura L. Elnitski 1 Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Rockville, Maryland, United States of America, 2 Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, Rockville, Maryland, United States of America A ‘‘bidirectional gene pair’’ comprises two adjacent genes whose transcription start sites are neighboring and directed away from each other. The intervening regulatory region is called a ‘‘bidirectional promoter.’’ These promoters are often associated with genes that function in DNA repair, with the potential to participate in the development of cancer. No connection between these gene pairs and cancer has been previously investigated. Using the database of spliced- expressed sequence tags (ESTs), we identified the most complete collection of human transcripts under the control of bidirectional promoters. A rigorous screen of the spliced EST data identified new bidirectional promoters, many of which functioned as alternative promoters or regulated novel transcripts. Additionally, we show a highly significant enrichment of bidirectional promoters in genes implicated in somatic cancer, including a substantial number of genes implicated in breast and ovarian cancers. The repeated use of this promoter structure in the human genome suggests it could regulate co-expression patterns among groups of genes. Using microarray expression data from 79 human tissues, we verify regulatory networks among genes controlled by bidirectional promoters. Subsets of these promoters contain similar combinations of transcription factor binding sites, i