Sequence-specific regulator Prdm14 safeguards mouse ESCs from entering extraembryonic endoderm fates

Abstract

Prdm14 is a PR-domain and zinc-finger protein whose expression is restricted to the pluripotent cells of the early embryo, embryonic stem cells (ESCs), and germ cells. Here, we show that Prdm14 safeguards mouse ESC (mESC) maintenance by preventing induction of extraembryonic endoderm (ExEn) fates. Conversely, Prdm14 overexpression impairs ExEn differentiation during embryoid body formation. Prdm14 occupies and represses genomic loci encoding ExEn differentiation factors, while also binding to and promoting expression of genes associated with mESC self-renewal. Prdm14-associated genomic regions substantially overlap those occupied by Nanog and Oct4, are enriched in a chromatin signature associated with distal regulatory elements and contain a unique DNA-sequence motif recognized by Prdm14 in vitro. Our work identifies a new member of the mESC transcriptional network, Prdm14, which plays a dual role as a context-dependent transcriptional repressor or activator.

How to make a primordial germ cell

“…Single cell transcriptome data of normal and mutant PGCs, combined with the information on the targets of BLIMP1 and AP2γ in P19EC, as well as of PRDM14 in ESCs (Ma et al, 2011), has revealed that the germ cell programme is executed by a high degree of cooperative activity between the three factors. This enables initiation of several programmes in early PGCs, including the repression of somatic genes.…”

Primordial Germ Cells in Mice

“…Prdm14-deficient cells cannot form embryonic germ cells (EGCs) in culture. Prdm14 may act as a sequence-specific transcriptional regulator and is essential for the pluripotency of mice and human embryonic stem (ES) cells (Tsuneyoshi et al 2008;Chia et al 2010;Ma et al 2011).…”

Mechanism and Reconstitution In Vitro of Germ Cell Development in Mammals

“…Prdm14 deficiency led to ablation in the (re)acquisition of potential pluripotency and epigenome reprogramming (Yamaji et al 2008). More recently, Prdm14 was shown to play a critical role for the naïve pluripotency of mouse embryonic stem cells (mESCs) by antagonizing fibroblast growth factor (FGF) signaling and repressing de novo DNA methylation machinery (Ma et al 2011;Yamaji et al 2013). Therefore, among the key molecular events for mPGC specification, these studies showed that epigenome reprogramming and (re)acquisition of potential pluripotency are regulated by Prdm14, whereas all of the key PGC events including repression of somatic programs are governed by Blimp1 (Fig.…”