Transcriptional and epigenetic control of early life cell fate decisions

Global epigenetic reprogramming of the parental genomes after fertilization ensures the establishment of genome organization permissive for cell specialization and differentiation during development. In this review, we highlight selected, well-characterized relationships between epigenetic factors and transcriptional cell fate regulators during the initial stages of mouse development.

Blastomeres of the mouse embryo are characterized by atypical and dynamic histone modification arrangements, noncoding RNAs and DNA methylation profiles. Moreover, asymmetries in epigenomic patterning between embryonic cells arise as early as the first cleavage, with potentially instructive roles during the first lineage allocations in the mouse embryo. Although it is widely appreciated that transcription factors and developmental signaling pathways play a crucial role in cell fate specification at the onset of development, it is increasingly clear that their function is tightly connected to the underlying epigenetic status of the embryonic cells in which they act.

Findings on the interplay between genetic, epigenetic and environmental factors during reprogramming and differentiation in the embryo are crucial for understanding the molecular underpinnings of disease processes, particularly tumorigenesis, which is characterized by global epigenetic rewiring and progressive loss of cellular identity.