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

• Published in: Stem cells (Dayton, Ohio) Vol. 39; no. 11; pp. 1435 - 1446
• Main Authors: Uranishi, Kousuke, Hirasaki, Masataka, Kitamura, Yuka, Mizuno, Yosuke, Nishimoto, Masazumi, Suzuki, Ayumu, Okuda, Akihiko
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-11-2021; Oxford University Press
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors - metabolism; Binding; Deoxyribonucleic acid; DNA; DNA - metabolism; Domains; Embryo cells; embryonic stem cells; Embryonic Stem Cells - metabolism; gene expression; gene targeting; Genes; Germ Cells; Meiosis; Meiosis - genetics; Mice; Molecular modelling; Mouse Embryonic Stem Cells; pluripotent stem cells; Scaffolding; Stem cell transplantation; Stem cells; Transcription activation; gene targeting; pluripotent stem cells; embryonic stem cells; gene expression
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.3433

Although the physiological meaning of the high potential of mouse embryonic stem cells (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 of Meiosin, which plays essential roles in meiotic entry with Stra8, revealing at least part of the molecular mechanisms that link negative and positive regulation of meiotic onset.
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 embryonic stem cells (ESCs), respectively. Here, we demonstrate that both Mga domains repress distinct sets of meiosis‐related genes in ESCs. Our data also identified Meiosin as a linchpin molecule between positive and negative regulations of meiotic onset.