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 ∼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.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Warnatz HJ,Querfurth R,Guerasimova A,Cheng X,Haas SA,Hufton AL,Manke T,Vanhecke D,Nietfeld W,Vingron M,Janitz M,Lehrach H,Yaspo MLdoi
10.1093/nar/gkq402subject
Has Abstractpub_date
2010-10-01 00:00:00pages
6112-23issue
18eissn
0305-1048issn
1362-4962pii
gkq402journal_volume
38pub_type
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