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Joint analysis of a compendium gene expression data and 5′‐untranslated mRNA regions points to a common cis‐regulatory region under epigenetic control
Author(s) -
Mrowka Ralf,
Blüthgen Nils,
Fähling Michael,
Steege Andreas,
Martinka Peter,
Brinkmeier Thomas,
Thiele Bernd J,
Persson Pontus B,
Patzak Andreas,
Holste Dirk
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1024.2
Subject(s) - biology , genetics , untranslated region , regulatory sequence , gene , translational efficiency , computational biology , epigenetics , messenger rna , gene expression , promoter , transcription (linguistics) , dna methylation , regulation of gene expression , translation (biology) , linguistics , philosophy
Untranslated regions located at the 5′ terminus (5′‐UTRs) of eukaryotic messenger RNAs (mRNAs) are often encoding functional cis‐regulatory sequence elements or structural features to modulate the rate of transcription, the stability of mRNAs or the translational initiation for protein synthesis. Elements that influence transcription are difficult to infer and have largely remained hidden. In an attempt to uncover candidate transcriptional regulatory elements that influence the level of gene expression, we systematically compared sequence similarities of 5′‐UTRs with the experimentally measured co‐expression of human genes across more than 1,200 publicly available microarray data. To this end, we employed a non‐heuristic algorithm for efficient exact matching of local sequence similarities, which is based on the mathematical Fourier transform. The algorithm was used to test oligonucleotides as candidates for transcriptional regulation of 5′‐UTRs. The most pronounced signal was localized at about 30 to 40 nucleotides downstream of the mRNA transcription start site, which were subsequently searched for overrepresented sequence motifs. Statistically significant enrichment of GC‐box motifs suggests a prominent role of DNA methylation, as one possible underlying epigenetic mechanism explaining the observed relationship between sequence similarity and co‐expression.