11.8 : Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory sequences of additional transcriptional regulators and induce their production. The expression of a particular phenotype in an organism is often under the control of one or two master transcription regulators. The significance of these regulators in the functioning of organisms and the expression of diseased phenotypes make them ideal targets for drug development research.

MEF2C is a master transcriptional regulator that is predominantly responsible for the development of breast cancer. It belongs to the Mef2 family of transcription activators responsible for cell differentiation and development. There are several characteristic features of MEF2C that demonstrate its function as a master transcription regulator. It consists of two DNA binding domains – Mef2 and MADS-box. The Mef2 domain is known for its high-affinity DNA binding and dimerization function. MEF2C also has binding sites for TEAD1, a co-regulator that is responsible for enhancing transcription; MAPK7, a transcription factor that regulates cell proliferation and differentiation; EP300, a transcription factor involved in regulation of cell growth and division; and several histone deacetylases, such as HDAC4, HDAC7, and HDAC9.

Experimental analysis has shown that MEF2C can directly regulate many genes responsible for the oncogenic phenotype. It can also indirectly regulate the phenotype by activating other transcription factors: 1896 genes and 2156 regulatory interactions at the second-order and 5852 genes and 18801 interactions at the third-order.