Transcriptional remodeling by OTX2 directs specification and patterning of mammalian definitive endoderm [CUTnTAG]

We discovered a role for the transcription factor OTX2 in formation of mouse definitive endoderm (DE). We used CUT&TAG to map H3K27ac- and H3K4me1-bound genomic regions and identify OTX2-bound enhancers during directed differentiation of EpiSCs to Primitive Streak (PS) intermediates and DE Mouse EpiSCs were converted to PS and DE. OTX2 was depleted for 21hrs at induction of each stage by dTAG13 treatment and OTX2-dependent H3K27ac and H3K4me1 binding sites were mapped using CUT&TAG.