Linking disease-associated genes to regulatory networks via promoter organization

S. Döhr, A. Klingenhoff, H. Maier, Hrabé M. de Angelis, T. Werner, Ralf Schneider

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)864-872
Number of pages9
JournalNucleic Acids Research
Volume33
Issue number3
DOIs
StatePublished - 2005
Externally publishedYes

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