The first lineage-specification event in the early embryo generates the inner cell mass (ICM), which later gives rise to the embryo proper, and the trophectoderm (TE), which then develops into extra-embryonic tissues. This fate decision is known to depend upon the activity of key chromatin modifiers but their precise mechanism of action remains mysterious. Now, Brian Hendrich and colleagues (p. ) show that CHD4, an ATP-dependent chromatin remodelling protein generally thought to participate in the NuRD complex to repress transcription, is essential for TE specification and ensures successful blastocyst implantation. Mechanistically, the authors show that CHD4 is required for TE specification independently of the NuRD complex. They further show that, in contrast to its role in somatic cells where it mediates cell cycle progression, CHD4 is not required for cell division but instead regulates apoptosis and maintains the expression of appropriate lineage markers, thus reducing the frequency of multi-lineage gene expression. By using single-cell transcriptional output, this study describes the temporal and molecular sequence of events leading to the first lineage commitment during embryogenesis.
