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The T-box transcription factor (TF) Eomesodermin/Tbr2 (Eomes) is essential for maintenance of the trophectoderm (TE) lineage, but the molecular mechanisms underlying this critical role remain obscure. Here, we show in trophoblast stem cells (TSCs) that Eomes partners with several TE-specific TFs as well as chromatin remodellers, including Brg1 and other subunits of the BAF complex. Degron-mediated Eomes protein depletion results in genome-wide loss of chromatin accessibility at TSC-specific loci. These overlap with a subset of sites that lose accessibility following Brg1 inhibition, suggesting that Eomes acts as a "doorstop" controlling TSC chromatin accessibility. Eomes depletion also causes transcriptional misregulation of TSC maintenance and early differentiation markers. An additional subset of Eomes-dependent genes encode intercellular/matricellular interaction and cytoskeletal components, likely explaining the implantation defects of Eomes-null embryos. Thus, Eomes promotes TE lineage maintenance by sustaining trophectoderm-specific chromatin accessibility, while promoting the gene regulatory networks that modulate expansion and cell behaviour during implantation.

Original publication

DOI

10.1038/s41467-025-60417-w

Type

Journal article

Journal

Nat Commun

Publication Date

31/05/2025

Volume

16

Keywords

T-Box Domain Proteins, Animals, Trophoblasts, Mice, Transcription Factors, Cell Lineage, Female, Ectoderm, Cell Differentiation, Gene Expression Regulation, Developmental, Nuclear Proteins, DNA Helicases, Chromatin, Embryo Implantation