Mediator complex dependent regulation of cardiac development and disease

Abstract

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality. The risk factors for CVD include environmental and genetic components. Human mutations in genes involved in most aspects of cardiovascular function have been identified, many of which are involved in transcriptional regulation. The Mediator complex serves as a pivotal transcriptional regulator that functions to integrate diverse cellular signals by multiple mechanisms including recruiting RNA polymerase II, chromatin modifying proteins and non-coding RNAs to promoters in a context dependent manner. This review discusses components of the Mediator complex and the contribution of the Mediator complex to normal and pathological cardiac development and function. Enhanced understanding of the role of this core transcriptional regulatory complex in the heart will help us gain further insights into CVD.

Figure 1

Model representing regulation of Mediator-dependent transcription The Mediator complex coordinates the input from signal-dependent transcription factors (TFs) to recruit RNA polymerase II (RNAPII) and regulate the expression of RNAPII-dependent genes. Chromatin modifiers (GCN5L and CBP/p300), non-coding RNAs including long non-coding RNAs (ncRNA-a) and microRNAs (miR-208a, miR-378 and 378∗), and elongation factors including P-TEFb converge at the Mediator complex to integrate cellular signals resulting in the activation or repression of transcription.