Cutting edge Seminar

 

Speaker:  Suzuki Ayumu  (Lecturer, Faculty of Medicine, Saitama Medical University)

Title:  The Role of MAX in Controlling Meiotic Gene Expression in Germ Cells and Early Embryonic Cells

 

 

 

※This seminar can also be attended through ZOOM. Please check the URL on “HIGO Cutting-Edge Seminar” at Moodle.

https://md.kumamoto-u.ac.jp/course/view.php?id=114380

 

Abstrac:

Meiosis, a specialized cell division process that halves ploidy and generates genetic diversity, is by itself evolutionarily conserved across all eukaryotes including yeast. However, the mechanisms that govern the entry into this process vary conspicuously among species, underpinning unique reproductive strategy of each species. Our research objective is to elucidate these processes that operate in mammals, particularly focusing on uncovering the role of MYC-associated factor X (MAX).

Previously, we discovered that knockout of Max in embryonic stem cells (ESCs) leads to the emergence of cells that morphologically resemble those of germ cells at early meiotic prophase (Suzuki et al., Nature Communications, 2016). In that study, we identified the PRC1.6 complex, which contains MAX and MGA, as the molecular entity that blocks meiosis-related genes from being expressed ectopically in ESCs. Recently, we demonstrated that the same complex, i.e., PRC1.6, also prevents meiosis-related genes from being expressed precociously in germ cells, using germ cell-specific Max knockout mice (Suzuki et al., Scientific Reports, 2024). Furthermore, our collaborative work elucidated that PRC1.6-mediated repression of meiosis-related genes in inner cell mass (ICM) cells of the blastocyst is a crucial prerequisite step to attain histone H3K9 methylation, and that such chromatin with H3K9 methylation functions as a scaffold for recruiting enzymes that endow DNA methylation to establish complete repression in the epiblast of the post-implantation embryo (Mochizuki et al., Nature Communications, 2021). These findings suggest that MAX contributes to the control of meiotic gene expression in both germ cells and early embryonic cells.

In this seminar, I will present our findings on the mechanisms by which MAX regulates meiosis, from our initial discoveries to our most recent work. In addition, I will present data about the role of MAX as a blockade of expression of 2-cell embryo-specific genes, which is our ongoing project.

 

References:

Suzuki A, et al. Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells. Nature Communications 7:11056 (2016)

Uranishi K, et al. Two DNA binding domains of MGA act in combination to suppress ectopic activation of meiosis-related genes in mouse embryonic stem cells. Stem Cells 39(11):1435-1446 (2021)

Mochizuki K, et al. Repression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing. Nature Communications 12:7020 (2021)

Suzuki A, et al. MAX controls meiotic entry in sexually undifferentiated germ cells. Scientific Reports 14:5236 (2024)