Epigenetics and differentiation of early embryonic lineages

Mammalian embryonic differentiation is intimately linking concurrent establishment of lineage specific transcriptional programs with buildup of matching epigenetic landscapes supporting them. Recently, single cell RNA-seq facilitated the construction of detailed transcriptional atlases describing gene expression programs in all embryonic lineages. We use in-vitro and in-vivo models to study the impact of different epigenetic regulators on the determination and stabilization of these lineages. First, we focus on DNA methylation, and provide new evidence for specific functions and previously unnoticed genomic preferences for the two de-novo DNA methyltransferases Dnmt3a/b in early germ layer commitment. Second, we use single cell Hi-C in early embryos to demonstrate exceptionally compact and previously undefined chromosomal structures in committed primitive erythrocytes and a large number of ectoderm and mesoderm specific long-range contacts between enhancers and promoters. We will discuss the how these findings and additional ongoing work shape our understanding of the function of epigenetic mechanisms in embryonic lineage choice and lineage commitment.