Methylation of histone H3K23 blocks DNA damage in pericentric heterochromatin during meiosis
Romeo Papazyan,
Ekaterina Voronina,
Jessica R Chapman,
Teresa R Luperchio,
Tonya M Gilbert,
Elizabeth Meier,
Samuel G Mackintosh,
Jeffrey Shabanowitz,
Alan J Tackett,
Karen L Reddy,
Robert S Coyne,
Donald F Hunt,
Yifan Liu,
Sean D Taverna
Affiliations
Romeo Papazyan
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
Ekaterina Voronina
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
Jessica R Chapman
Department of Chemistry, University of Virginia, Charlottesville, United States
Teresa R Luperchio
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
Tonya M Gilbert
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
Elizabeth Meier
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
Samuel G Mackintosh
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, United States
Jeffrey Shabanowitz
Department of Chemistry, University of Virginia, Charlottesville, United States
Alan J Tackett
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, United States
Karen L Reddy
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
Robert S Coyne
Department of Genomic Medicine, J. Craig Venter Institute, Rockville, United States
Donald F Hunt
Department of Chemistry, University of Virginia, Charlottesville, United States; Department of Pathology, University of Virginia, Charlottesville, United States
Yifan Liu
Department of Pathology, University of Michigan Medical School, Ann Arbor, United States
Sean D Taverna
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
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.
