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  Functional analysis and identification of cis-regulatory elements of human chromosome 21 gene promoters

Warnatz, H. J., Querfurth, R., Guerasimova, A., Cheng, X., Haas, S. A., Hufton, A. L., et al. (2010). Functional analysis and identification of cis-regulatory elements of human chromosome 21 gene promoters. Nucleic Acids Research, 38(18), 6112-6123. doi:10.1093/nar/gkq402.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7A35-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7A36-8
Genre: Journal Article
Alternative Title : Nucleic Acids Res

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 Creators:
Warnatz, H. J.1, Author              
Querfurth, R.2, Author              
Guerasimova, A.3, Author              
Cheng, X.4, Author
Haas, S. A.4, Author
Hufton, A. L., Author
Manke, T.2, Author              
Vanhecke, D., Author
Nietfeld, W.3, Author              
Vingron, M.5, Author              
Janitz, M.3, Author              
Lehrach, H.3, Author              
Yaspo, M. L.1, Author              
Affiliations:
1Human Chromosome 21 (Marie-Laure Yaspo), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479652              
2Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433547              
3Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
4Max Planck Society, ou_persistent13              
5Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              

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Free keywords: Cell Line; Chromosomes, Human, Pair 21; Cloning, Molecular; Gene Expression; Humans; Promoter Regions, Genetic; RNA Polymerase II/metabolism; Regulatory Elements, Transcriptional
 Abstract: 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 approximately 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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Language(s): eng - English
 Dates: 2010-10
 Publication Status: Published in print
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Title: Nucleic Acids Research
  Alternative Title : Nucleic Acids Res
Source Genre: Journal
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Pages: - Volume / Issue: 38 (18) Sequence Number: - Start / End Page: 6112 - 6123 Identifier: ISSN: 1362-4962 (Electronic) 0305-1048 (Linking) %R gkq402 [pii] 10.1093/nar/gkq402