Two DNA binding domains of Mga act in combination to suppress ectopic activation of meiosis-related genes in mouse embryonic stem cells

Abstract

Mouse embryonic stem cells (ESCs) have high potential for meiotic entry, like germ cells. Although the physiological meaning of this potential is not known, it is certain that a rigid safeguarding system is required to prevent ectopic onset of meiosis. PRC1.6, a non-canonical PRC1, is known for its suppression of precocious and ectopic meiotic onset in germ cells and ESCs, respectively, in which MGA has important roles in DNA binding as well as in constructing the complex as a scaffolding component. As a salient feature, MGA bears two distinct DNA-binding domains termed bHLHZ and T-box. However, how these features contribute to the functions of PRC1.6, particularly in the repression of meiotic genes, remains largely obscure. Here, we demonstrated that both DNA binding domains of Mga repress distinct sets of genes in murine ESCs, and substantial numbers of meiosis-related genes are included in both gene sets. In addition, our data demonstrated that both DNA binding domains of Mga, in particular bHLHZ, are crucially involved in repressing the expression of Meiosin, which plays essential roles in meiotic entry in collaboration with Stra8, revealing at least part of the molecular mechanisms that link negative and positive regulation of meiotic onset.