TH2A is phosphorylated at meiotic centromere by Haspin

Area of Science:

• Epigenetics and Chromatin Biology
• Reproductive Biology and Meiosis
• Molecular Cell Biology

Background:

• Histone phosphorylation is a critical regulator of cell division, particularly during mitosis and meiosis.
• A specific phosphorylation on TH2A (pTH2A), a germ cell-specific H2A variant, has been identified in mouse spermatids and early embryos.
• The precise role and regulation of pTH2A at meiotic centromeres remain largely unexplored.

Purpose of the Study:

• To investigate the localization and function of pTH2A at centromeres during mouse oocyte and spermatocyte meiosis.
• To identify the kinase responsible for pTH2A formation in vivo.
• To assess the physiological significance of pTH2A in fertility and meiotic progression.

Main Methods:

• Immunofluorescence microscopy to detect pTH2A localization in spermatocytes and oocytes.
• In vivo studies using pTH2A-deficient mice (Th2a T127A mutation).
• Treatment with a Haspin inhibitor to assess the impact on meiosis.
• Analysis of fertility and meiotic phenotypes in wild-type and mutant mice, including aged oocytes.

Main Results:

• pTH2A was detected at centromeres in metaphase I spermatocytes and oocytes.
• Haspin was identified as the kinase responsible for pTH2A formation in vivo.
• Oocytes treated with a Haspin inhibitor exhibited severe meiotic defects.
• Conversely, pTH2A-deficient mice showed no fertility or meiotic defects in oocytes or spermatogenesis.
• pTH2A levels decreased significantly in aged oocytes, potentially linked to centromeric cohesins.

Conclusions:

• Haspin-mediated TH2A phosphorylation (pTH2A) is a novel component of the meiotic centromere.
• While crucial for oocyte meiosis, pTH2A is dispensable for male fertility and spermatogenesis in mice.
• The regulation and accumulation of pTH2A are influenced by factors like centromeric cohesins and age.