What Makes a Transcriptional Master Regulator? A Systems Biology Approach

Abstract

Gene regulatory networks present a wide variety of dynamical responses to intrinsic and extrinsic perturbations. An outstanding case of such coordinated responses is that of transcriptional amplification cascades, in which activation of a few key-responsive transcription factors (termed master regulators) leads to a large series of transcriptional activation events. Recent studies have pointed to the protein called myocyte enhancing factor 2C (MEF2C) as being one of such master regulators involved in the pathogenesis of primary breast cancer. A systems biology analysis of the transcriptional regulation activity of MEF2C and its target genes, has revealed that this molecule induces collective responses leading to system-level gene expression deregulation and carcinogenesis. We found extensive evidence for this. Being this the case, one may wonder what set of physicochemical, structural and thermodynamic constrains need to be satisfied if a protein is to become a transcription factor, and moreover a master regulator? Some hints will be discussed.