Elements of Computational Systems Biology

12

FROM DNA MOTIFS TO GENE NETWORKS: A REVIEW OF PHYSICAL INTERACTION MODELS

Panayiotis V. Benos

Departments of Computational Biology and Biomedical Informatics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

Alain B. Tchagang

Department of Computational Biology, School of Medicine,University of Pittsburgh, Pittsburgh, PA, USA

12.1 INTRODUCTION

Understanding the interactions between biomolecules within a cell and between cells and their environment is one of the major challenges in computational biology. Although every cell in an organism contains the same genetic material, its expression profile depends on the tissue type, developmental stage, and the extracellular signals it receives at the given point in time. Cells exert various ways to regulate the expression of their genes. Chromatin structure, for example, can make large parts of the genome transcriptionally silent or potentially active. Also, posttranscriptional and posttranslational mechanisms can influence the amount and the activity of the available proteins and noncoding genes in a cell. The best studied mechanism for gene expression control, however, is the transcription regulation at the individual gene level. Transcription factor (TF) proteins recognize short DNA “signals” (typically 6–15 base pairs long) in the vicinity of the genes' transcription start sites (TSSs) and enhance or suppress their expression. These DNA signals are commonly referred to as transcription-factor binding sites (TFBSs) ...