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

MGA bearing two distinct DNA-binding domains is a scaffolding component of PRC1.6 that prevents precocious and ectopic onset of meiosis in germ cells and ESCs, respectively. Here, we demonstrate that both Mga domains repress distinct sets of meiosis-related genes in ESCs. Our data also identifiedMeiosin as a linchpin molecule between positive and negative regulations of meiotic onset. AbstractAlthough the physiological meaning of the high potential of mouse ESCs for meiotic entry is not understood, 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. MGA, a scaffolding component of PRC1.6, bears two distinct DNA-binding domains termed bHLHZ and T-box. However, it is unclear how this feature contributes to the functions of PRC1.6. Here, we demonstrated that both domains repress distinct sets of genes in murine ESCs, but substantial numbers of meiosis-related genes are included in both gene sets. In addition, our data demonstrated that bHLHZ is crucially involved in repressing the expression ofMeiosin, which plays essential roles in meiotic entry withStra8, revealing at least part of the molecular mechanisms that link negative and positive regulation of meiotic onset.© AlphaMed Press 2021Significance StatementPRC1.6, one of non-canonical PRC1 is known to function as a safeguard preventing precocious and ectopic onset o...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research