Isolation and characterization of Suv39h2, a second histone H3 methyltransferase gene that displays testis-specific expression

Isolation and characterization of Suv39h2, a second histone H3 methyltransferase gene that displays testis-specific expression
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DOI:
10.1128/mcb.20.24.9423-9433.2000
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发表时间:
2000-12-01
影响因子:
5.3
通讯作者:
Jenuwein, T
Jenuwein, T
中科院分区:
生物学2区
文献类型:
--
作者:
O'Carroll, D;Scherthan, H;Jenuwein, T

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高阶染色质与表观遗传基因控制和染色体的功能组织有关。我们最近发现了小鼠(Suv39h1)和人(SW39H1)组蛋白H3赖氨酸9选择性甲基转移酶(Suv39h HMTases),并表明它们调节体细胞染色质动力学。我们在这里描述了第二个小鼠基因Suv39h2的分离、染色体分配和表征。与Suv39h1一样,SIlv39h2编码的H3 HMTase与Suv39h1有59%的相似性,但不同之处在于存在一个高度碱性的N端。利用荧光原位杂交和单倍型分析,Suv39h2位点定位于小鼠2号染色体的亚着丝粒区,而Suv39h1位点位于小鼠X染色体的尖端。值得注意的是,尽管两个Suv39h基因座在小鼠胚胎发育过程中表现出重叠的表达谱,但Suv39h2转录本在成年睾丸中仍有特异性表达。Suv39h2蛋白在精子发生过程中的免疫定位表明,从瘦素期到圆形精子期,在异染色质上的分布丰富。此外,Suv39h2特异地在性染色体(XY小体)的染色质上积累,这些染色体在减数分裂的第一个前期经历转录沉默。这些数据与Suv39h1和Suv39h2在小鼠发育过程中的冗余酶作用一致,并表明Suv39h2 HMTase在组织减数分裂异染色质方面具有额外的功能,甚至可能给雄性生殖系带来表观遗传印记。
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.