Format

Send to

Choose Destination
Elife. 2014 Aug 26;3:e02996. doi: 10.7554/eLife.02996.

Methylation of histone H3K23 blocks DNA damage in pericentric heterochromatin during meiosis.

Author information

1
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, United States Center for Epigenetics, The Johns Hopkins University School of Medicine, Baltimore, United States.
2
Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Balitmore, United States Center for Cell Dynamics, The Johns Hopkins University School of Medicine, Baltimore, United States.
3
Department of Chemistry, University of Virginia, Charlottesville, United States.
4
Center for Epigenetics, The Johns Hopkins University School of Medicine, Baltimore, United States Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, United States.
5
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, United States.
6
Department of Genomic Medicine, J. Craig Venter Institute, Rockville, United States.
7
Department of Chemistry, University of Virginia, Charlottesville, United States Department of Pathology, University of Virginia, Charlottesville, United States.
8
Department of Pathology, University of Michigan Medical School, Ann Arbor, United States.
9
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, United States Center for Epigenetics, The Johns Hopkins University School of Medicine, Baltimore, United States staverna@jhmi.edu.

Abstract

Despite the well-established role of heterochromatin in protecting chromosomal integrity during meiosis and mitosis, the contribution and extent of heterochromatic histone posttranslational modifications (PTMs) remain poorly defined. Here, we gained novel functional insight about heterochromatic PTMs by analyzing histone H3 purified from the heterochromatic germline micronucleus of the model organism Tetrahymena thermophila. Mass spectrometric sequencing of micronuclear H3 identified H3K23 trimethylation (H3K23me3), a previously uncharacterized PTM. H3K23me3 became particularly enriched during meiotic leptotene and zygotene in germline chromatin of Tetrahymena and C. elegans. Loss of H3K23me3 in Tetrahymena through deletion of the methyltransferase Ezl3p caused mislocalization of meiosis-induced DNA double-strand breaks (DSBs) to heterochromatin, and a decrease in progeny viability. These results show that an evolutionarily conserved developmental pathway regulates H3K23me3 during meiosis, and our studies in Tetrahymena suggest this pathway may function to protect heterochromatin from DSBs.

KEYWORDS:

DNA damage; Tetrahymena thermophila; chromatin; histones; meiosis; methylation

PMID:
25161194
PMCID:
PMC4141274
DOI:
10.7554/eLife.02996
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center