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          Institute: MPI für molekulare Genetik     Collection: Department of Computational Molecular Biology     Display Documents

ID: 447521.0, MPI für molekulare Genetik / Department of Computational Molecular Biology
Short ultraconserved promoter regions delineate a class of preferentially expressed alternatively spliced transcripts.
Authors:Rödelsperger, Christian; Köhler, Sebastian; Schulz, Marcel H.; Manke, Thomas; Bauer, Sebastian; Robinson, Peter N.
Date of Publication (YYYY-MM-DD):2009-08-04
Title of Journal:Genomics
Journal Abbrev.:Genomics
Issue / Number:5
Start Page:308
End Page:316
Copyright:2009 Elsevier Inc. All rights reserved.
Review Status:not specified
Audience:Experts Only
Abstract / Description:Ultraconservation has been variously defined to describe sequences that have remained identical or nearly so over long periods of evolution to a degree that is higher than expected for sequences under typical constraints associated with protein-coding sequences, splice sites, or transcription factor binding sites. Most intergenic ultraconserved elements (UCE) appear to be tissue-specific enhancers, whereas another class of intragenic UCEs is involved in regulation of gene expression by means of alternative splicing. In this study we define a set of 2827 short ultraconserved promoter regions (SUPR) in 5 kb upstream regions of 1268 human protein-coding genes using a definition of 98% identity for at least 30 bp in 7 mammalian species.

Our analysis shows that SUPRs are enriched in genes playing a role in regulation and development. Many of the genes having a SUPR-containing promoter have additional alternative promoters that do not contain SUPRs. Comparison of such promoters by CAGE tag, EST, and Solexa read analysis revealed that SUPR-associated transcripts show a significantly higher mean expression than transcripts associated with non-SUPR-containing promoters. The same was true for the comparison between all SUPR-associated and non-SUPR-associated transcripts on a genome-wide basis.

SUPR-associated genes show a highly significant tendency to occur in regions that are also enriched for intergenic short ultraconserved elements (SUE) in the vicinity of developmental genes. A number of predicted transcription factor binding sites (TFBS) are overrepresented in SUPRs and SUEs, including those for transcription factors of the homeodomain family, but in contrast to SUEs, SUPRs are also enriched in core-promoter motifs. These observations suggest that SUPRs delineate a distinct class of ultraconserved sequences.
Free Keywords:Promoter;
Alternative splicing;
Digital gene expression;
Comment of the Author/Creator:Corresponding author: Peter N. Robinson
Institute for Medical Genetics, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
External Publication Status:published
Document Type:Article
Communicated by:Martin Vingron
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Institute for Medical Genetics, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany;
2.Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany;
3.International Max-Planck Research School for Computational Biology and Scientific Computing, Berlin, Germany.
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