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Regulatory modules shared within gene classes as well as across gene classes can be detected by the same in silico approach

A. Klingenhoff¹, K. Frech¹, T. Werner^1,2

¹Genomatix Software GmbH, Karlstraße 55, D-80333 München, Germany
²GSF-National Research Center for Environment and Health, Institute of Mammalian Genetics, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany
E-mail: klingenhoff@gsf.de, frech@gsf.de, werner@gsf.de


Edited by E. Wingender; received April 19, 2000; revised July 24, 2000; accepted July 25, 2000

Abstract

Transcriptional regulation depends on the binding of transcription factors to their corresponding binding sites. The response to cellular signals is often mediated by the cooperative binding of transcription factors to well defined regulatory modules consisting of at least two transcription factor binding sites. Such regulatory modules can be responsible for the common regulation of genes within a gene class or confer a common function to promoters belonging to different gene classes. We developed in silico models representing a common framework of potential regulatory sites specific for one promoter class (actins). We also generated models for two different functional promoter modules both of which confer responsiveness to tumor necrosis factor (TNF) and interferon (IFN) to a variety of promoters. All models exhibited high selectivity, e.g. the mammalian muscle actin promoter model produced no false negatives in a database search.

Key words: transcription factor binding sites, promoter analysis, promoter classification, database search, muscle actin genes, common regulation, promoter modules