Isolation and Characterization of Suv39h2, a Second Histone H3 Methyltransferase Gene That Displays Testis-Specific Expression

Abstract

Higher-order chromatin has been implicated in epigenetic gene control and in the functional organization of chromosomes. We have recently discovered mouse (Suv39h1) and human (SUV39H1) histone H3 lysine 9-selective methyltransferases (Suv39h HMTases) and shown that they modulate chromatin dynamics in somatic cells. We describe here the isolation, chromosomal assignment, and characterization of a second murine gene, Suv39h2. Like Suv39h1,Suv39h2 encodes an H3 HMTase that shares 59% identity with Suv39h1 but which differs by the presence of a highly basic N terminus. Using fluorescent in situ hybridization and haplotype analysis, the Suv39h2 locus was mapped to the subcentromeric region of mouse chromosome 2, whereas the Suv39h1 locus resides at the tip of the mouse X chromosome. Notably, although bothSuv39h loci display overlapping expression profiles during mouse embryogenesis, Suv39h2 transcripts remain specifically expressed in adult testes. Immunolocalization of Suv39h2 protein during spermatogenesis indicates enriched distribution at the heterochromatin from the leptotene to the round spermatid stage. Moreover, Suv39h2 specifically accumulates with chromatin of the sex chromosomes (XY body) which undergo transcriptional silencing during the first meiotic prophase. These data are consistent with redundant enzymatic roles for Suv39h1 and Suv39h2 during mouse development and suggest an additional function of the Suv39h2 HMTase in organizing meiotic heterochromatin that may even impart an epigenetic imprint to the male germ line.

ACKNOWLEDGMENTS

We thank Gotthold Schaffner, Robert Kurzbauer, and Ivan Botto for sequence analysis and oligonucleotide synthesis; Alexander Schleiffer for database searches on the C. elegansC15H11.5 ORF; Meinrad Busslinger for advice on the exon/intron organization of the genomic Suv39h2 clone; Jean-Louis Guénet (Pasteur Institute, Paris, France) for his gift of WMP mice; Cécile Mignon-Ravix for help in the FISH analysis; Prim B. Singh (The Roslin Institute, Roslin, Midlothian, United Kingdom) for α-M31 (HP1β) antibodies; Christa Heyting (Wageningen, The Netherlands) for α-Scp3 antibodies; H.-J. Garchon (Hopital Necker, Paris, France) for α-Xmr antibodies; and Karl Mechtler for Suv39h2 antiserum purification.

This work was supported by the IMP through Boehringer Ingelheim and by grants from by the Austrian Research Promotion Fund to T.J., the Deutsche Forschungsgemeinschaft (grant number DFG #350/8-2) to H.S., the Medical Research Council (United Kingdom) to S.D.M.B., and the ARC (Association pour la Recherche sur le Cancer) to M.G.M.