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Döhr, S. ; Klingenhoff, A.* ; Maier, H. ; Hrabě de Angelis, M. ; Werner, T.* ; Schneider, R.

Linking disease-associated genes to regulatory networks via promoter organization.

Nucleic Acids Res. 33, 864-872 (2005)
Verlagsversion Volltext DOI
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 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
Quellenangaben Band: 33, Heft: 3, Seiten: 864-872 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Begutachtungsstatus Peer reviewed