Developmental cell fate specification is a unidirectional process that can be reverted in response to injury or experimental reprogramming. Whether differentiation and de-differentiation trajectories intersect mechanistically is unclear. Here, we performed comparative screening in lineage-related mouse nave embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), and identified the constitutively expressed zinc finger transcription factor (TF) Zfp281 as a bi-directional regulator of cell state interconversion. We showed that subtle chromatin occupancy changes in differentiated cells translate into binding and activation of the histone H3 lysine 9 (H3K9) methyltransferase Ehmt1 and the zinc finger TF Zic2 at enhancers and promoters. Genetic gain and loss of function experiments confirmed a critical role of Ehmt1 and Zic2 downstream of Zfp281 both in driving exit from the ESC state, and in restricting EpiSC reprogramming. Our study reveals that cell type-invariant chromatin association of Zfp281 provides an interaction platform for remodeling the cis-regulatory network underlying cellular plasticity. SOURCE: Joerg Betschinger (joerg.betschinger@fmi.ch) -  Friedrich Miescher Institute

Pluto Bioinformatics

GSE131015: Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2 (RNA-seq)