Dynamics of DOT1L localization and H3K79 methylation during meiotic prophase I in mouse spermatocytes Journal Article

   

Authors:	Ontoso, D.; Kauppi, L.; Keeney, S.; San-Segundo, P. A.
Article Title:	Dynamics of DOT1L localization and H3K79 methylation during meiotic prophase I in mouse spermatocytes
Abstract:	During meiotic prophase I, interactions between maternal and paternal chromosomes, under checkpoint surveillance, establish connections between homologs that promote their accurate distribution to meiotic progeny. In human, faulty meiosis causes aneuploidy resulting in miscarriages and genetic diseases. Meiotic processes occur in the context of chromatin; therefore, histone post-translational modifications are expected to play important roles. Here, we report the cytological distribution of the evolutionarily conserved DOT1L methyltransferase and the different H3K79 methylation states resulting from its activity (mono-, di- and tri-methylation; H3K79me1, me2 and me3, respectively) during meiotic prophase I in mouse spermatocytes. In the wild type, whereas low amounts of H3K79me1 are rather uniformly present throughout prophase I, levels of DOT1L, H3K79me2 and H3K79me3 exhibit a notable increase from pachynema onwards, but with differential subnuclear distribution patterns. The heterochromatic centromeric regions and the sex body are enriched for H3K79me3. In contrast, H3K79me2 is present all over the chromatin, but is largely excluded from the sex body despite the accumulation of DOT1L. In meiosis-defective mouse mutants, the increase of DOT1L and H3K79me is blocked at the same stage where meiosis is arrested. H3K79me patterns, combined with the cytological analysis of the H3.3, γH2AX, macroH2A and H2A.Z histone variants, are consistent with a differential role for these epigenetic marks in male mouse meiotic prophase I. We propose that H3K79me2 is related to transcriptional reactivation on autosomes during pachynema, whereas H3K79me3 may contribute to the maintenance of repressive chromatin at centromeric regions and the sex body. © 2013 Springer-Verlag.
Keywords:	controlled study; unclassified drug; nonhuman; protein function; protein localization; animal cell; chromosome structure; mouse; pachytene; spermatocyte; cytology; mouse mutant; protein protein interaction; molecular dynamics; animal experiment; wild type; transgenic mouse; methyltransferase; epigenetics; chromatin; histone h3; cell cycle arrest; cellular distribution; autosome; bioinformatics; histone h2a; histone h2ax; lysine; knockout mouse; meiotic prophase i; gamma histone h2ax; sex chromosome; histone methylation; sex body; male; article; dot1 like enzyme; h3k79me protein; h3k79me1 protein; h3k79me2 protein; h3k79me3 protein; histone 3.3; histone h2az; lysine 79; heterochromatic centromeric region; histone 3 at lysine 79 dimethylation; histone 3 at lysine 79 monomethylation; histone 3 at lysine 79 trimethylation
Journal Title:	Chromosoma
Volume:	123
Issue:	1-2
ISSN:	0009-5915
Publisher:	Springer
Date Published:	2014-03-01
Start Page:	147
End Page:	164
Language:	English
DOI:	10.1007/s00412-013-0438-5
PROVIDER:	scopus
PMCID:	PMC3969405
PUBMED:	24105599
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84897560870&partnerID=40&md5=1f169a7e55a064fd011e4af7e08558dc
Notes:	Export Date: 1 May 2014 -- CODEN: CHROA -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/50185