| Functional analysis and identification of cis-regulatory elements of human chromosome 21 gene promoters. | |
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MedLine Citation:
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PMID: 20494980 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Given the inherent limitations of in silico studies relying solely on DNA sequence analysis, the functional characterization of mammalian promoters and associated cis-regulatory elements requires experimental support, which demands cloning and analysis of putative promoter regions. Focusing on human chromosome 21, we cloned 182 gene promoters of 2500 bp in length and conducted reporter gene assays on transfected-cell arrays. We found 56 promoters that were active in HEK293 cells, while another 49 promoters could be activated by treatment of cells with Trichostatin A or depletion of serum. We observed high correlations between promoter activities and endogenous transcript levels, RNA polymerase II occupancy, CpG islands and core promoter elements. Truncation of a subset of 62 promoters to ∼500 bp revealed that truncation rarely resulted in loss of activity, but rather in loss of responses to external stimuli, suggesting the presence of cis-regulatory response elements within distal promoter regions. In these regions, we found a strong enrichment of transcription factor binding sites that could potentially activate gene expression in the presence of stimuli. This study illustrates the modular functional architecture of chromosome 21 promoters and helps to reveal the complex mechanisms governing transcriptional regulation. |
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Authors:
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Hans-Jörg Warnatz; Robert Querfurth; Anna Guerasimova; Xi Cheng; Stefan A Haas; Andrew L Hufton; Thomas Manke; Dominique Vanhecke; Wilfried Nietfeld; Martin Vingron; Michal Janitz; Hans Lehrach; Marie-Laure Yaspo |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-21 |
Journal Detail:
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Title: Nucleic acids research Volume: 38 ISSN: 1362-4962 ISO Abbreviation: Nucleic Acids Res. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-13 Completed Date: 2010-11-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0411011 Medline TA: Nucleic Acids Res Country: England |
Other Details:
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Languages: eng Pagination: 6112-23 Citation Subset: IM |
Affiliation:
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Department for Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany. warnatz@molgen.mpg.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line Chromosomes, Human, Pair 21* Cloning, Molecular Gene Expression Humans Promoter Regions, Genetic* RNA Polymerase II / metabolism Regulatory Elements, Transcriptional* |
| Chemical | |
Reg. No./Substance:
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EC 2.7.7.-/RNA Polymerase II |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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