2019 The Company of Biologists

The development of an organism is regulated by tightly coordinated changes in gene expression. From zygotic gene activation, through to lineage specification and organogenesis, and into postnatal physiology and disease, broad programs of gene activation and repression are deployed in a carefully orchestrated manner. Eventually, the deployment of such developmental programs results in the formation of hundreds of different cell types, all containing the same DNA. Based on this, Conrad Waddington proposed more than half a century ago that development is an example of his epigenetic landscape.

DNA-binding transcription factors (TFs) are the leading drivers of these dynamic and cell type-specific gene regulatory networks, but TFs must function within the topological and physical constraints presented by the dense packing of DNA in chromatin, and within the context of histone modifications, DNA methylation and other aspects of chromatin-mediated regulation. All of these aspects of gene regulation – from TF binding sites, to nucleosomes, to topologically associated domains – are emerging as interlocked layers of developmentally important gene regulation.

levels of chromatin regulation that impact developmental gene regulation

levels of gene regulation

TF interactions with chromatin, histone modifications, chromatin remodelers, DNA methylation, RNA-binding proteins and 3D organization of the genome.

 limb patterning, cardiac differentiation, intestinal development, heart regeneration, zygotic genome activation, control of pluripotency, retrotransposon regulation, cell cycle regulation, dosage compensation, and maintenance of the body plan.