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Linking disease-associated genes to regulatory networks via promoter organization.
Nucleic Acids Res. 33, 864-872 (2005)
Pathway- or disease-associated genes may participate in more than one transcriptional co-regulation network. Such gene groups can be readily obtained by literature analysis or by high-throughput techniques such as microarrays or protein-interaction mapping. We developed a strategy that defines regulatory networks by in silico promoter analysis, finding potentially co-regulated subgroups without a priori knowledge. Pairs of transcription factor binding sites conserved in orthologous genes (vertically) as well as in promoter sequences of co-regulated genes (horizontally) were used as seeds for the development of promoter models representing potential co-regulation. This approach was applied to a Maturity Onset Diabetes of the Young (MODY)-associated gene list, which yielded two models connecting functionally interacting genes within MODY-related insulin/glucose signaling pathways. Additional genes functionally connected to our initial gene list were identified by database searches with these promoter models. Thus, data-driven in silico promoter analysis allowed integrating molecular mechanisms with biological functions of the cell.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
INSULIN-RECEPTOR SUBSTRATE-1; SEQUENCE SIMILARITY; FUNCTIONAL PROMOTER; SYSTEMS BIOLOGY; MICE LACKING; MOUSE GENOME; CELL-CYCLE; IDENTIFICATION; TRANSCRIPTION; ELEMENTS
ISSN (print) / ISBN
0305-1048
e-ISSN
1362-4962
Journal
Nucleic Acids Research
Quellenangaben
Volume: 33,
Issue: 3,
Pages: 864-872
Publisher
Oxford University Press
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Experimental Genetics (IEG)