MEIOSIN Directs the Switch from Mitosis to Meiosis in Mammalian Germ Cells

Abstract

Highlights d MEIOSIN plays an essential role in meiotic initiation both in male and female d MEIOSIN and STRA8 bind and activate meiotic genes d MEIOSIN and STRA8 play a central role in cell-cycle switching from mitosis to meiosis d Temporal expression of MEIOSIN is required for meiotic entry decision

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

“…Stra8 is not a direct target of the negative regulation of PRC1.6 (Endoh et al, 2017;Suzuki et al, 2016). Interestingly, however, our data indicated that Meiosin, which has recently been shown to encode an indispensable partner for Stra8 (Ishiguro et al, 2020), is a direct downstream target of PRC1.6 whose expression is elevated profoundly and marginally in ΔbHLHZ and ΔT ESCs, respectively (see Table S3). Histone modification analyses by ChIP-seq as well as locus-specific ChIP-qPCR strongly supports the notion that Meiosin, but not Stra8, was subjected to Mga (bHLHZ domain)-dependent regulation of PRC1.6 ( Fig.…”

“…Our data also revealed that bHLHZ-dependent regulation of meiosis-related genes almost exclusively reflected the role of Mga within PRC1.6, while T-box-dependent regulation of Mga was relatively less tightly linked to PRC1.6. Moreover, our data identified a molecular link between the positive and negative regulation of meiotic entry in which meiotic entry promoted by the retinoic acid (RA)-Stra8 axis (Anderson et al, 2008;Baltus et al, 2006;Dokshin et al, 2013;Mark et al, 2008) is further potentiated by de-repression of Meiosin gene, which encodes an indispensable partner for Stra8 (Ishiguro et al, 2020) upon impairment of the transcriptional repressing activity of PRC1.6 that is known to occur at the onset of meiosis in germ cells (Suzuki et al, 2016).…”

Phosphorylation of the Anaphase Promoting Complex activator CDH1/FZR regulates the transition from Meiosis I to Meiosis II in mouse male germ cell

“…Ab5535), rabbit anti-CyclinB1(IB, 1:1000, Santa Cruz: sc-595), mouse anti-PLK1(IB, 1:1000, Abcam ab17056), rabbit anti-SYCP1 (IF, 1:1000, Abcam ab15090), rabbit anti-γH2AX (IF, 1:1000, Abcam ab2893), rat anti-TRA98 (IF, 1:1000, ab82527), rabbit anti-CENPC (Ishiguro et al, 2011), rabbit anti-MEIKIN (IF, 1:1000) (Kim et al, 2015), rat anti-SYCP3 (Ishiguro et al, 2020), guinea pig anti-H1t (IF, 1:2000, kindly provided by Marry Ann Handel).…”

Nutrient restriction, inducer of yeast meiosis, induces mammalian meiotic initiation

“…1H; table S4). Nutrient restriction appears to play four roles on the expression of key meiotic genes by: 1) inducing a subset of meiotic gene expression that was not regulated by RA, such as Rad21l; 2) initiating the activation of a subset of meiotic genes, which was further enhanced by RA, such as Zfp541; 3) synergizing with RA to induce the activation of a subset of meiosis gene expressions, such as Sycp1, Sycp3,Mei1,Msh5,and Stag3;and 4) augmenting the expression of a subset of meiotic genes induced by RA, including Dmc1, Smc1b, Ugt8a, Stag3, Hormad1, as well as Gm4969, which encodes MEIOSIN, a transcriptional cofactor for STRA8 required for meiotic prophase program 17 . Notably, many meiotic genes whose expression is STRA8-dependent require nutrient restriction ( Fig.…”