Pluto Bioinformatics

GSE86817: Nono, a novel bivalent domain factor, regulates Erk signaling and mouse embryonic stem cell pluripotency [RNA-Seq]

Bulk RNA sequencing

Here we report that Nono instead functions as a chromatin regulator cooperating with Erk to regulate mESC pluripotency. We demonstrate that Nono loss leads to robust self-renewing mESCs with enhanced expression of Nanog and Klf4, epigenome and transcriptome re-patterning to a ground-like state with global reduction of H3K27me3 and DNA methylation resembling the Erk inhibitor PD03 treated mESCs and 2i (both GSK and Erk kinase inhibitors)-induced ground state. Mechanistically, Nono and Erk co-bind at a subset of development-related, bivalent genes. Ablation of Nono compromises Erk activation and RNA polymerase II C-terminal Domain serine 5 phosphorylation, and while inactivation of Erk evicts Nono from chromatin, revealing reciprocal regulation. Furthermore, Nono loss results in a compromised activation of its target bivalent genes upon differentiation and the differentiation itself. These findings reveal an unanticipated role of Nono in collaborating with Erk signaling to regulate the integrity of bivalent domain and mESC pluripotency. SOURCE: Li Wenjing (13110700025@fudan.edu.cn) - Laboratory of Epigenetics Fudan University