Expression of BLIMP1/PRMT5 and concurrent histone H2A/H4 arginine 3 dimethylation in fetal germ cells, CIS/IGCNU and germ cell tumors.
Expression of BLIMP1/PRMT5 and concurrent histone H2A/H4 arginine 3 dimethylation in fetal germ cells, CIS/IGCNU and germ cell tumors.
复制标题
DOI：
10.1186/1471-213x-8-106
复制
发表时间：
2008-11-07
影响因子：
--
通讯作者：
Schorle, Hubert
中科院分区：
文献类型：
--
作者：
Eckert, Dawid;Biermann, Katharina;Nettersheim, Daniel;Gillis, Ad J. M.;Steger, Klaus;Jaeck, Hans-Martin;Mueller, Annette M.;Looijenga, Leendert H. J.;Schorle, Hubert
大多数睾丸生殖细胞肿瘤起源于未分类的小管内生殖细胞瘤（IGCNU，也称为原位癌），其被认为起源于转化的原始生殖细胞（PGC）/生殖细胞，即胎儿生殖细胞。IGCNU和卵巢癌的分子谱分析显示与胎儿生殖细胞/生殖细胞的表达谱相似。在小鼠PGCs中，Blimp 1和Prmt 5的表达和相互作用导致组蛋白H2 A和H4的精氨酸3二甲基化。这施加表观遗传修饰，导致小鼠PGC中的转录抑制，使它们能够在迁移期间逃避体细胞分化程序，同时表达多能性标记。在本研究中，我们发现，BLIMP 1和PRMT 5的表达和精氨酸二甲基化组蛋白H2 A和H4检测在人类男性生殖细胞在妊娠第12-19周，表明这种机制在人类胎儿生殖细胞发育的作用，以及。此外，BLIMP 1/PRMT 5和组蛋白H2 A和H4精氨酸3二甲基化在IGCNU和大多数腺瘤中存在，而在胚胎性癌（EC）和其他非腺瘤性肿瘤中下调。这些数据揭示了小鼠和人PGC之间标记物表达和组蛋白修饰的相似性。此外，我们推测组蛋白H2 A和H4精氨酸3二甲基化可能是IGCNU和腺瘤维持未分化状态的机制，而这些组蛋白修饰的丢失导致在非腺瘤性肿瘤中观察到的体细胞分化。
Most testicular germ cell tumors arise from intratubular germ cell neoplasia unclassified (IGCNU, also referred to as carcinoma in situ), which is thought to originate from a transformed primordial germ cell (PGC)/gonocyte, the fetal germ cell. Analyses of the molecular profile of IGCNU and seminoma show similarities to the expression profile of fetal germ cells/gonocytes. In murine PGCs, expression and interaction of Blimp1 and Prmt5 results in arginine 3 dimethylation of histone H2A and H4. This imposes epigenetic modifications leading to transcriptional repression in mouse PGCs enabling them to escape the somatic differentiation program during migration, while expressing markers of pluripotency. In the present study, we show that BLIMP1 and PRMT5 were expressed and arginine dimethylation of histones H2A and H4 was detected in human male gonocytes at weeks 12–19 of gestation, indicating a role of this mechanism in human fetal germ cell development as well. Moreover, BLIMP1/PRMT5 and histone H2A and H4 arginine 3 dimethylation was present in IGCNU and most seminomas, while downregulated in embryonal carcinoma (EC) and other nonseminomatous tumors. These data reveal similarities in marker expression and histone modification between murine and human PGCs. Moreover, we speculate that the histone H2A and H4 arginine 3 dimethylation might be the mechanism by which IGCNU and seminoma maintain the undifferentiated state while loss of these histone modifications leads to somatic differentiation observed in nonseminomatous tumors.