EOMES establishes mesoderm and endoderm differentiation potential through SWI/SNF-mediated global enhancer remodeling.

Mammalian pluripotent cells first segregate into neuroectoderm (NE), or mesoderm and endoderm (ME), characterized by lineage-specific transcriptional programs and chromatin states. To date, the relationship between transcription factor activities and dynamic chromatin changes that guide cell specification remains ill-defined. In this study, we employ mouse embryonic stem cell differentiation toward ME lineages to reveal crucial roles of the Tbx factor Eomes to globally establish ME enhancer accessibility as the prerequisite for ME lineage competence and ME-specific gene expression.

Author Correction: Eomes and Brachyury control pluripotency exit and germ-layer segregation by changing the chromatin state.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Eomes and Brachyury control pluripotency exit and germ-layer segregation by changing the chromatin state.

The first lineage specification of pluripotent mouse epiblast segregates neuroectoderm (NE) from mesoderm and definitive endoderm (ME) by mechanisms that are not well understood. Here we demonstrate that the induction of ME gene programs critically relies on the T-box transcription factors Eomesodermin (also known as Eomes) and Brachyury, which concomitantly repress pluripotency and NE gene programs. Cells deficient in these T-box transcription factors retain pluripotency and differentiate to NE lineages despite the presence of ME-inducing signals transforming growth factor β (TGF-β)/Nodal and Wnt.