PRDM14 Is a Unique Epigenetic Regulator Stabilizing Transcriptional Networks for Pluripotency.

Yoshiyuki Seki

doi:10.3389/fcell.2018.00012

Abstract

PR-domain containing protein 14 (PRDM14) is a site-specific DNA-binding protein and is required for establishment of pluripotency in embryonic stem cells (ESCs) and primordial germ cells (PGCs) in mice. DNA methylation status is regulated by the balance between de novo methylation and passive/active demethylation, and global DNA hypomethylation is closely associated with cellular pluripotency and totipotency. PRDM14 ensures hypomethylation in mouse ESCs and PGCs through two distinct layers, transcriptional repression of the DNA methyltransferases Dnmt3a/b/l and active demethylation by recruitment of TET proteins. However, the function of PRDM14 remains unclear in other species including humans. Hence, here we focus on the unique characteristics of mouse PRDM14 in the epigenetic regulation of pluripotent cells and primordial germ cells. In addition, we discuss the expression regulation and function of PRDM14 in other species compared with those in mice.

Highlights

Specialty section: This article was submitted to Epigenomics and Epigenetics, a section of the journal Frontiers in Cell and Developmental
DNA methylation levels and Dnmt3a/b/l expression are consistently maintained at high levels in Prdm14-deficient embryonic stem cells (ESCs) even in the presence of 2i plus leukemia inhibitory factor (LIF), and PRDM14 directly binds to the upstream region of Dnmt3a/b/l and represses the transcription of these genes (Yamaji et al, 2013; Okashita et al, 2014)
These findings indicate that PRDM14 is responsible for global hypomethylation through transcriptional repression of Dnmt3a/b/l in groundstate ESCs (Leitch et al, 2013)

Summary

Introduction

Specialty section: This article was submitted to Epigenomics and Epigenetics, a section of the journal Frontiers in Cell and Developmental. PR-domain containing protein 14 (PRDM14) is a site-specific DNA-binding protein and is required for establishment of pluripotency in embryonic stem cells (ESCs) and primordial germ cells (PGCs) in mice.

Results

Conclusion