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Cell. 2015 Nov 5;163(4):920-33. doi: 10.1016/j.cell.2015.10.002. Epub 2015 Oct 29.

Histone H3 Threonine Phosphorylation Regulates Asymmetric Histone Inheritance in the Drosophila Male Germline.

Author information

1
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
2
HHMI, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
3
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA. Electronic address: xchen32@jhu.edu.

Abstract

A long-standing question concerns how stem cells maintain their identity through multiple divisions. Previously, we reported that pre-existing and newly synthesized histone H3 are asymmetrically distributed during Drosophila male germline stem cell (GSC) asymmetric division. Here, we show that phosphorylation at threonine 3 of H3 (H3T3P) distinguishes pre-existing versus newly synthesized H3. Converting T3 to the unphosphorylatable residue alanine (H3T3A) or to the phosphomimetic aspartate (H3T3D) disrupts asymmetric H3 inheritance. Expression of H3T3A or H3T3D specifically in early-stage germline also leads to cellular defects, including GSC loss and germline tumors. Finally, compromising the activity of the H3T3 kinase Haspin enhances the H3T3A but suppresses the H3T3D phenotypes. These studies demonstrate that H3T3P distinguishes sister chromatids enriched with distinct pools of H3 in order to coordinate asymmetric segregation of "old" H3 into GSCs and that tight regulation of H3T3 phosphorylation is required for male germline activity.

PMID:
26522592
PMCID:
PMC4636931
DOI:
10.1016/j.cell.2015.10.002
[Indexed for MEDLINE]
Free PMC Article

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