Distant conserved sequences flanking endothelial-specific promoters contain tissue-specific DNase-hypersensitive sites and over-represented motifs

John A Bernat; Gregory E Crawford; Aleksey Y Ogurtsov; Francis S Collins; David Ginsburg; Alexey S Kondrashov

doi:10.1093/hmg/ddl133

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Distant conserved sequences flanking endothelial-specific promoters contain tissue-specific DNase-hypersensitive sites and over-represented motifs

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Distant conserved sequences flanking endothelial-specific promoters contain tissue-specific DNase-hypersensitive sites and over-represented motifs

John A Bernat, Gregory E Crawford, Aleksey Y Ogurtsov, Francis S Collins, David Ginsburg and Alexey S Kondrashov

Human molecular genetics, Vol.15(13), pp.2098-2105

07/01/2006

DOI: 10.1093/hmg/ddl133

PMID: 16723375

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Abstract

The transcriptional regulation of genes is a complex process, particularly for genes exhibiting a tissue-specific pattern of expression. We studied 28 genes that are expressed primarily in endothelial cells, another 28 genes that are expressed highly, but not exclusively, in cultured endothelial cells, and three control sets, consisting of genes not expressed in endothelium, genes expressed in neural tissues and housekeeping genes. For each gene, we identified conserved non-coding sequences (CNSs) of lengths 50 to >1000 nucleotides, located within the upstream intergenic region (from 500 to as far as 200 000 nucleotides upstream from the transcription start) or within the first intron. As a functional test, we assayed the CNSs from the set of endothelial cell-specific genes (EC-CNSs) for DNase hypersensitivity. Among 262 distant EC-CNSs, 33% are hypersensitive (HS) in endothelial cells, whereas only 16% are HS in control fibroblasts. A search for short sequence patterns revealed a number of motifs which are over-represented in EC-CNSs relative to CNSs from the control gene sets. In particular, the motif SAGGAAR is strongly and consistently over-represented among EC-CNSs, and is more over-represented in HS CNSs than in non-HS CNSs. CNSs which contain this motif are no closer to the promoter than an average CNS. This motif contains the core element of binding sites from the Ets family of transcription factors. Thus, one or several factors from this family may play a key role in the regulation of endothelial gene expression.

Details

Title: Subtitle: Distant conserved sequences flanking endothelial-specific promoters contain tissue-specific DNase-hypersensitive sites and over-represented motifs
Creators: John A Bernat - Department of Human Genetics and
Gregory E Crawford - National Human Genome Research Institute and
Aleksey Y Ogurtsov - National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD 20892, USA
Francis S Collins - National Human Genome Research Institute and
David Ginsburg - Department of Human Genetics and
Alexey S Kondrashov - National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD 20892, USA
Resource Type: Journal article
Publication Details: Human molecular genetics, Vol.15(13), pp.2098-2105
Publisher: Oxford University Press
DOI: 10.1093/hmg/ddl133
PMID: 16723375
ISSN: 0964-6906
eISSN: 1460-2083
Language: English
Date published: 07/01/2006
Academic Unit: Stead Family Department of Pediatrics; Medical Genetics and Genomics
Record Identifier: 9984093234702771

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