Elements of Computational Systems Biology

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THE IMPACT OF WHOLE GENOME IN SILICO SCREENING FOR NUCLEAR RECEPTOR-BINDING SITES IN SYSTEMS BIOLOGY

Carsten Carlberg and Merja Heinäaniemi

Life Sciences Research Unit, University of Luxembourg, Luxembourg

13.1 INTRODUCTION

Each individual human gene is under the control of a large set of transcription factors that can bind upstream and downstream of its transcription start site (TSS) [1]. These sites typically arrange into collections of neighboring sites, the so-called modules or enhancers. Modules of transcription factors that act on focused genomic regions have been shown to be far more effective than individual factors on isolated locations and can act from large distances up to hundreds of thousands of base pairs. In an ideal case, such transcription factor modules can be identified by parallel and comparative analysis of their binding sites. Here, bioinformatics approaches can be of great help, in case they can predict the actions of the transcription factors precisely enough [2].

13.2 NUCLEAR RECEPTORS

Nuclear receptors (NRs) form a superfamily with 48 human members, of which most have the special property to be ligand-inducible [3, 4]. This property has attracted interest in the NR family as possible therapeutical targets. NRs are the best characterized representatives of approximately 3000 different mammalian proteins that are involved in transcriptional regulation in human tissues [5]. NRs modulate genes that affect processes as diverse as reproduction, development, ...