Spatiotemporal regulation of enhancers during cardiogenesis

Abstract

With the advance in chromatin immunoprecipitation followed by high-throughput sequencing, there has been a dramatic increase in our understanding of distal enhancer function. In the developing heart, the identification and characterisation of such enhancers have deepened our knowledge of the mechanisms of transcriptional regulation that drives cardiac differentiation. With next-generation sequencing techniques becoming widely accessible, the quantity of data describing the genome-wide distribution of cardiac-specific transcription factor and chromatin modifiers has rapidly increased and it is now becoming clear that the usage of enhancers is highly dynamic and complex, both during the development and in the adult. The identification of those enhancers has revealed new insights into the transcriptional mechanisms of how tissue-specific gene expression patterns are established, maintained, and change dynamically during development and upon physiological stress.

Keywords: Development; Embryonic stem cell; Heart; Transcription.

Fig. 1

Mechanism of transcriptional regulation by successive binding of MEIS1 and NKX2–5 on cardiac enhancers. NKX2–5 and MEIS1 are able to bind in vitro on a DNA motif (GTGNTGACAG) which is an overlapping-binding site for the two transcription factors. As cardiac progenitors differentiate in the mouse embryo, they successively experience high levels of MEIS1 expression in the secondary heart field (grey) followed by high levels of NKX2–5 expression in the heart tube (red). Cardiac enhancers with an overlapping-binding site for MEIS1 and NKX2–5 are bound successively by those factors