The role of master regulators in gene regulatory networks

TL;DR

This paper investigates how master regulators like MEF2C influence gene expression dynamics and contribute to carcinogenesis through integrative genomic analysis and modeling of transcriptional responses.

Contribution

It provides new insights into the role of MEF2C as a master regulator in gene regulatory networks and its impact on cancer-related gene expression deregulation.

Findings

MEF2C significantly influences gene expression patterns in breast cancer.

Transcriptional bursts and nonlinear cascades are linked to malignant phenotypes.

Master regulators induce collective responses leading to carcinogenesis.

Abstract

Gene regulatory networks present a wide variety of dynamical responses to intrinsic and extrinsic perturbations. Arguably, one of the most important of such coordinated responses is the one of amplification cascades, in which activation of a few key-responsive transcription factors (termed master regulators, MRs) lead to a large series of transcriptional activation events. This is so since master regulators are transcription factors controlling the expression of other transcription factor molecules and so on. MRs hold a central position related to transcriptional dynamics and control of gene regulatory networks and are often involved in complex feedback and feedforward loops inducing non-trivial dynamics. Recent studies have pointed out to the myocyte enhancing factor 2C (MEF2C, also known as MADS box transcription enhancer factor 2, polypeptide C) as being one of such master regulators involved in the pathogenesis of primary breast cancer. In this work, we perform an integrative genomic analysis of the transcriptional regulation activity of MEF2C and its target genes to evaluate to what extent are these molecules inducing collective responses leading to gene expression deregulation and carcinogenesis. We also analyzed a number of induced dynamic responses, in particular those associated with transcriptional bursts, and nonlinear cascading to evaluate the influence they may have in malignant phenotypes and cancer.