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



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ID: 536286.0, MPI für molekulare Genetik / Department of Computational Molecular Biology
Functional analysis and identification of cis-regulatory elements of human chromosome 21 gene promoters
Authors:Warnatz, H. J.; Querfurth, R.; Guerasimova, A.; Cheng, X.; Haas, S. A.; Hufton, A. L.; Manke, T.; Vanhecke, D.; Nietfeld, W.; Vingron, M.; Janitz, M.; Lehrach, H.; Yaspo, M. L.
Language:English
Date of Publication (YYYY-MM-DD):2010-10
Title of Journal:Nucleic Acids Research
Journal Abbrev.:Nucleic Acids Res
Volume:38
Issue / Number:18
Start Page:6112
End Page:6123
Copyright:© 2010 Oxford University Press
Review Status:not specified
Audience:Experts Only
Abstract / Description: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.
Free Keywords:Cell Line; Chromosomes, Human, Pair 21; Cloning, Molecular; Gene Expression; Humans; Promoter Regions, Genetic; RNA Polymerase II/metabolism; Regulatory Elements, Transcriptional
External Publication Status:published
Document Type:Article
Communicated by:Martin Vingron
Affiliations:MPI für molekulare Genetik
External Affiliations:Department of Biomedicine, University Basel, Mattenstrasse 28, 4058 Basel, Switzerland
School of Biotechnology and Biomolecular Sciences,
The University of New South Wales, Sydney NSW 2052, Australia
Identifiers:ISSN:1362-4962 (Electronic) 0305-1048 (Linking) %R gkq4... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=... [ID No:2]
DOI:10.1093/nar/gkq402 [ID No:3]
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