Regulation of Vertebrate Conduction System Development

Excerpt

The cardiac conduction system (CCS) consists of distinctive components that initiate and conduct the electrical impulse required for the coordinated contraction of the cardiac chambers. The development of the CCS involves complex regulatory networks of transcription factors that act in stage, tissue and dose-dependent manners. As disrupted function or expression of these factors may lead to disorders in the development or function of components of the CCS associated with heart failure and sudden death, it is crucial to understand the molecular and cellular mechanisms underlying their complex regulation. Here, we discuss the regulation of genes driving CCS-specific gene expression and demonstrate the complexity of the mechanisms governing their regulatory networks. The three-dimensional conformation of chromatin has recently been recognized as an important regulatory layer, shaping the genome in regulatory domains and physically wiring gene promoters to their regulatory sequences. Knowledge of the mechanisms by which distal-acting regulatory sequences exert their function to drive tissue-specific gene expression and understanding how the three-dimensional chromatin landscape is involved in this regulation will increase our understanding of how disease-associated genomic variation affects the function of such sequences.