Epigenetic modulation through BRD8 impairs conversion of primed EpiSCs to naïve ESCs [RNA-Seq]

Epigenetic control of cell type is a critical determinant in cell type stability and permissive differentiation. However, the epigenetic control mechanisms are not well understood. Here, we explore the epigenetic control of the conversion of primed mouse EpiSCs to naïve mouse ESCs as a mimic for early stages of embryonic development. Whilst the conversion of naïve to primed state is relatively permissive and mimics a normal developmental program, the reverse process, primed to naïve is inefficient in the absence of transgenes, which suggests the presence of potent epigenetic barriers that resist this artificial dedifferentiation. Here, we identify the histone acetylation reader BRD8 as a one-way barrier that blocks the conversion of primed to naïve cells. BRD8 works by maintaining histone acetylation on promoters and transcribed gene bodies and it’s absence promotes the formation of heterochromatin. RNA-seq of the EpiSCs undergoing a primed to naïve conversion at the indicated days. The EpiSCs were transfected with shRNAs targetting Brd8 or Igf2bp2.