Phosphorylation of Histone H3 Is Required for Proper Chromosome Condensation and Segregation

TLDR

Phosphorylation of histone H3 at serine 10 occurs during mitosis in diverse eukaryotes and correlates closely with mitotic and meiotic chromosome condensation. The study aimed to elucidate the role of H3 phosphorylation by generating Tetrahymena strains expressing only a mutant H3 (S10A) protein. The authors constructed Tetrahymena strains where the sole histone H3 gene carried an S10A mutation to abolish phosphorylation. Loss of H3 serine‑10 phosphorylation caused defective chromosome condensation and segregation in mitotic micronuclei, leading to chromosome loss, and also impaired meiotic chromosome condensation and transmission, demonstrating its essential role in chromosome dynamics.

Abstract

Phosphorylation of histone H3 at serine 10 occurs during mitosis in diverse eukaryotes and correlates closely with mitotic and meiotic chromosome condensation. To better understand the function of H3 phosphorylation in vivo, we created strains of Tetrahymena in which a mutant H3 gene (S10A) was the only gene encoding the major H3 protein. Although both micronuclei and macronuclei contain H3 in typical nucleosomal structures, defects in nuclear divisions were restricted to mitotically dividing micronuclei; macronuclei, which are amitotic, showed no defects. Strains lacking phosphorylated H3 showed abnormal chromosome segregation, resulting in extensive chromosome loss during mitosis. During meiosis, micronuclei underwent abnormal chromosome condensation and failed to faithfully transmit chromosomes. These results demonstrate that H3 serine 10 phosphorylation is causally linked to chromosome condensation and segregation in vivo and is required for proper chromosome dynamics.