Novel polymorphisms in the SUV39H2 histone methyltransferase and the risk of lung cancer
CARCINOGENESIS
Authors: Yoon, Kyong-Ah; Hwangbo, Bin; Kim, Il-Jin; Park, Sohee; Kim, Hee Sun; Kee, Hyun Jung; Lee, Jong Eun; Jang, Yeun Kyu; Park, Jae-Gahb; Lee, Jin Soo
Abstract
Histone H3 lysine 9 (H3-K9) methylation and DNA methylation are important features of mammalian heterochromatin. Suppressor of variegation 3-9 homolog 2 (SUV39H2) is the histone methyltransferase that is required to methylate H3-K9, leading to transcriptional repression or silencing of target genes. In this study, we investigated the association of SUV39H2 polymorphisms and the risk of lung cancer. From the results of PCR direct sequencing, eight single nucleotide polymorphisms (SNPs) of SUV39H2 were identified in Korean population. In a hospital-based study of 346 lung cancer patients and 423 healthy controls, a novel SNP in the 3 '-UTR of SUV39H2 (1624 G -> C) was associated with a statistically significant increase in lung cancer risk. Compared to the G/G genotype, genotypes with 1624C allele (G/C + C/C) significantly increased the susceptibility to lung cancer with adjusted odds ratio (AOR) of 2.63 (95% confidence interval (CI)= 1.10-6.29) for ever-smokers, especially in the older age group (age >= 55 years). Specifically, the variant genotype of 1624SNP was significantly associated with an increased risk of squamous cell carcinoma (AOR, 3.52; 95% CI = 1.13-9.45) in the older age group, while no significant association was found in patients with other histology. This study provided the first evidence that a novel SUV39H2 polymorphism may be an important predictive marker for lung cancer susceptibility for the smokers.
Isolation and characterization of Suv39h2, a second histone H3 methyltransferase gene that displays testis-specific expression
MOLECULAR AND CELLULAR BIOLOGY
Authors: O'Carroll, D; Scherthan, H; Peters, AHFM; Opravil, S; Haynes, AR; Laible, G; Rea, S; Schmid, M; Lebersorger, A; Jerratsch, M; Sattler, L; Mattei, MG; Denny, P; Brown, SDM; Schweizer, D; Jenuwein, T
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 (SW39H1) 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, SIlv39h2 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 both Suv39h 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.