Division of Reproduction Genetics, Department of, Gynaecol. Endocrinology & Infertility Disorders, Women Hospital, University of Heidelberg, Germany.
Department of Gynaecol. Endocrinology & Infertility Disorders, Women Hospital, University of Heidelberg, Germany.
Reprod Fertil. 2021 Jun 7;2(2):151-160. doi: 10.1530/RAF-20-0049. eCollection 2021 Apr.
The Ubiquitous Transcribed Y ( a.k.a. ) AZFa candidate gene on the human Y chromosome and its paralog on the X chromosome, (a.k.a. ), encode a histone lysine demethylase removing chromatin H3K27 methylation marks at genes transcriptional start sites for activation. Both proteins harbour the conserved Jumonji C (JmjC) domain, functional in chromatin metabolism, and an extended N-terminal tetratricopeptide repeat (TPR) block involved in specific protein interactions. Specific antisera for human UTY and UTX proteins were developed to distinguish the expression of both proteins in human germ cells by immunohistochemical experiments on appropriate tissue sections. In the male germ line, UTY was expressed in the fraction of A spermatogonia located at the basal membrane, probably including spermatogonia stem cells. UTX expression was more spread in all spermatogonia and in early spermatids. In female germ line, UTX expression was found in the primordial germ cells of the ovary. UTY was also expressed during fetal male germ cell development, whereas UTX expression was visible only at distinct gestation weeks. Based on these results and the conserved neighboured location of and in Yq11 found in mammals of distinct lineages, we conclude that such as is part of the Azoospermia factor a (AZFa) locus functioning in human spermatogonia to support the balance of their proliferation-differentiation rate before meiosis. Comparable UTY and DDX3Y expression was also found in gonadoblastoma and dysgerminoma cells found in germ cell nests of the dysgenetic gonads of individuals with disorders of sexual development and a Y chromosome in karyotype (DSD-XY). This confirms that AZFa overlaps with GBY the Gonadoblastoma susceptibility Y locus, and includes the gene.
AZFa Y genes are involved in human male germ cells development and support gonadoblastoma (germ cell tumour precursor cells) in the aberrant germ cells of the gonads of females with genetic disorders of sexual development. The AZFa gene on the male Y chromosome is equivalent to on the female X chromosome. These genes are involved in removing gene regulators to enable activation of other genes (i.e. removal of histone methylation known as epigenetic modifications). We wanted to learn the function of UTY and UTX in developing sperm and eggs in human tissues and developed specific antibodies to detect both proteins made by these genes. Both UTY and UTX proteins were detected in adult and fetal sperm precursor cells (spermatogonia). UTX was detected in egg precursor cells (primordial germ cells). UTY was detected in gonadoblastoma and dysgerminoma tumour cells (germ cell tumours originating from genetic disorders of sexual development due to having a Y chromosome). Based on our study, we conclude that UTY is not only part of AZFa, but also of GBY the overlapping gonadoblastoma susceptibility Y region.
人类 Y 染色体上普遍转录的 Y（又称 AZFa 候选基因）及其在 X 染色体上的同源基因（又称）编码一种组蛋白赖氨酸去甲基酶，可去除基因转录起始位点处染色质 H3K27 甲基化标记，从而激活基因。这两种蛋白质都具有保守的 Jumonji C（JmjC）结构域，该结构域在染色质代谢中具有功能，并且具有扩展的 N 端四肽重复（TPR）结构域，参与特定的蛋白质相互作用。针对人类 UTY 和 UTX 蛋白开发了特异性抗体，以便通过适当组织切片的免疫组织化学实验来区分这两种蛋白在人类生殖细胞中的表达。在男性生殖细胞中，UTY 在位于基底膜的 A 精原细胞亚群中表达，可能包括精原干细胞。UTX 在所有精原细胞和早期精母细胞中的表达更为广泛。在女性生殖细胞中，UTX 在卵巢的原始生殖细胞中表达。在男性胎儿生殖细胞发育过程中也检测到 UTY 的表达，而 UTX 的表达仅在特定的妊娠周可见。基于这些结果以及在不同谱系的哺乳动物中发现的 Yq11 上的和的保守相邻位置，我们得出结论， （如）是参与人类精原细胞减数分裂前增殖分化率平衡的无精子症因子 a（AZFa）基因座的一部分。在性发育障碍个体的退化性腺中的生殖细胞巢中的生殖细胞瘤和发育不良性生殖细胞瘤细胞中也发现了类似的 UTY 和 DDX3Y 表达，这些个体的核型中存在 Y 染色体（DSD-XY）。这证实了 AZFa 与 GBY（生殖细胞瘤易感性 Y 基因座）重叠，并包含基因。
AZFa Y 基因参与人类男性生殖细胞的发育，并支持性发育障碍女性性腺中异常生殖细胞的生殖细胞瘤（生殖细胞肿瘤前体细胞）。男性 Y 染色体上的 AZFa 基因与女性 X 染色体上的相同。这些基因参与去除基因调节剂，以激活其他基因（即去除称为表观遗传修饰的组蛋白甲基化）。我们希望了解 UTY 和 UTX 在人类组织中发育精子和卵子的功能，并开发了特异性抗体来检测这些基因产生的两种蛋白质。在成年和胎儿精原细胞（精原细胞）中均检测到 UTY 和 UTX 蛋白。在卵子前体细胞（原始生殖细胞）中检测到 UTX。在性腺细胞瘤和发育不良性生殖细胞瘤肿瘤细胞（由于存在 Y 染色体而导致性发育障碍的遗传疾病起源的生殖细胞肿瘤）中检测到 UTY。基于我们的研究，我们得出结论，UTY 不仅是 AZFa 的一部分，也是重叠的生殖细胞瘤易感性 Y 区 GBY 的一部分。
