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Embryonic stem cells (ESCs) can adopt lineage-specific gene-expression programs by stepwise exposure to defined factors, resulting in the generation of functional cell types. Bulk and single-cell-based assays were employed to catalog gene expression, histone modifications, chromatin conformation, and accessibility transitions in ESC populations and individual cells acquiring a presomitic mesoderm fate and undergoing further specification toward myogenic and neurogenic lineages. These assays identified cis -regulatory regions and transcription factors presiding over gene-expression programs occurring at defined ESC transitions and revealed the presence of heterogeneous cell populations within discrete ESC developmental stages. The datasets were employed to identify previously unappreciated genomic elements directing the initial activation of Pax7 and myogenic and neurogenic gene-expression programs. This study provides a resource for the discovery of genomic and transcriptional features of pluripotent, mesoderm-induced ESCs and ESC-derived cell lineages. [Display omitted] • Transcriptional and epigenetics characterization of ESCs exiting pluripotency • Presomitic mesoderm gene programs and chromatin accessibility at single-cell resolution • Single-cell multiomics of ESCs acquiring neurogenic and myogenic fates • Identification of an enhancer directing Pax7 and neurogenic and myogenic gene programs Khateb et al. provide bulk and single-cell transcriptional, epigenetic, and chromatin accessibility profiling of ESCs induced to acquire presomitic mesoderm, myogenic, and neurogenic fates and identify a Pax7 enhancer directing transcription in myogenic and neurogenic precursors. [ABSTRACT FROM AUTHOR]

Chromatin remodelers are ATP-dependent machines responsible for directionally shifting nucleosomes along DNA. We are interested in defining which elements of the chromodomain helicase DNA-binding protein 1 (Chd1) remodeler are necessary and sufficient for sliding nucleosomes. This work focuses on the polypeptide segment that joins the ATPase motor to the C-terminal DNA-binding domain. We identify amino acid positions outside the ATPase motor that, when altered, dramatically reduce nucleosome sliding ability and yet have only ~3-fold reduction in ATPase stimulation by nucleosomes. These residues therefore appear to play a role in functionally coupling ATP hydrolysis to nucleosome sliding, and suggest that the ATPase motor requires cooperation with external elements to slide DNA past the histone core. [ABSTRACT FROM AUTHOR]