Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity for Pluripotency and Reprogramming [RNA-Seq]

Super-enhancers (SEs) are large clusters of transcriptional enhancers that are co-occupied by multiple lineage specific transcription factors driving expression of genes that define cell identity. In embryonic stem cells (ESCs), SEs are highly enriched for Oct4, Sox2, and Nanog in the enhanceosome assembly and express enhancer RNAs (eRNAs). We sought to dissect the molecular control mechanism of SE activity and eRNA transcription for pluripotency and reprogramming. Starting from a protein interaction network surrounding Sox2, a key pluripotency and reprogramming factor that guides the ESC-specific enhanceosome assembly and orchestrates the hierarchical transcriptional activation during the final stage of reprogramming, we discovered Tex10 as a novel pluripotency factor that is evolutionally conserved and functionally significant in ESC self-renewal, early embryo development, and reprogramming. Tex10 is enriched at SEs in a Sox2-dependent manner and coordinates histone acetylation and DNA demethylation of SEs. Our study sheds new light on epigenetic control of SE activity for cell fate determination. Overall design: RNA sequencing analysis was performed in mouse embryonic stem cells with Luciferase and Tex10 knockdown. RNA-seq Experiments were carry out in two biological replicates.

4

Ding J, Huang X, Shao N, Zhou H, Lee DF, Faiola F, Fidalgo M, Guallar D, Saunders A, Shliaha PV, Wang H, Waghray A, Papatsenko D, Sánchez-Priego C, Li D, Yuan Y, Lemischka IR, Shen L, Kelley K, Deng H, Shen X, Wang J