Phosphorylation of threonine 3 on histone H3 by Haspin kinase is required for meiosis I in mouse oocytes

Abstract

Meiosis I (MI), the division that generates haploids, is prone to errors that lead to aneuploidy in females. Haspin is a kinase that phosphorylates histone H3 on threonine 3 thereby recruiting Aurora kinase B (AURKB) and the chromosomal passenger complex (CPC) to kinetochores to regulate mitosis. Haspin and AURKC, an AURKB homolog, are enriched in germ cells, yet their significance in regulating MI are not fully understood. Using inhibitors and overexpression approaches, we show a role for Haspin during MI in mouse oocytes. Haspin-perturbed oocytes display abnormalities in chromosome morphology and alignment, improper kinetochore-microtubule attachments at metaphase I, and aneuploidy at metaphase II. Unlike in mitosis, kinetochore localization remained intact while the distribution of the CPC along chromosomes was absent. The meiotic defects of Haspin inhibition were similar to oocytes where AURKC was inhibited, suggesting that correction of microtubule attachments during MI require AURKC along chromosome arms rather than at kinetochores. Our data implicate Haspin as a regulator of the CPC and chromosome segregation during MI while highlighting important differences in how chromosome segregation is regulated between MI and mitosis.