Evolutionary diversification of SPANX-N sperm protein gene structure and expression.

Evolutionary diversification of SPANX-N sperm protein gene structure and expression.
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DOI:
10.1371/journal.pone.0000359
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发表时间:
2007-04-04
期刊:
影响因子:
3.7
通讯作者:
Larionov, Vladimir
Larionov, Vladimir
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kouprina, Natalay;Noskov, Vladimir N.;Pavlicek, Adam;Collins, N. Keith;Bortz, Pamela D. Schoppee;Ottolenghi, Chris;Loukinov, Dmitri;Goldsmith, Paul;Risinger, John I.;Kim, Jung-Hyun;Westbrook, V. Anne;Solomon, Gregory;Sounders, Hanna;Herr, John C.;Jurka, Jerzy;Lobanenkov, Victor;Schlessinger, David;Larionov, Vladimir

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X染色体中与核相关的精子蛋白(SPAN)基因在两个亚家族中聚簇在Xq 27处,SPAN-A/D和SPAN-N。SPAN-A/D是类人猿特有的,并且被很好地表征。在人科动物谱系中,1700万年前的SPAN-N产生了SPAN-A/D。鉴于所提出的作用,在精子发生中的斯潘X基因,我们已经扩展到斯潘X-N基因的进化,变异,表达调控和精子内定位的研究。通过免疫荧光分析,SPAN-N蛋白仅定位于减数分裂后的精子细胞中,如SPAN-A/D。但与斯潘X-A/D相反,斯潘X-N存在于所有射出的精子中,而不仅仅是在一个亚群中,位于顶体中,而不是核膜中,并且在几种非配子发生的成人组织以及许多癌症中以低水平表达。与MAGE-A1和NY-ESO-1类似,在SPAN启动子中存在CTCF及其睾丸特异性旁腺BORIS的结合位点表明,它们在精子发生中的激活是由BORIS程序性取代CTCF介导的。基于CpG的相对密度,在非配子发生组织中与SPAN-A/D相比,SPAN-N的更广泛表达可能归因于启动子甲基化的差异。我们的研究结果表明,最近在人科动物中重复的斯潘X基因伴随着不同的定位斯潘X-N蛋白在减数分裂后的精子和额外的表达在几个非性腺组织。这表明在人科动物中,SPAN基因家族具有相应的功能多样性。因此,斯潘X蛋白提供了独特的目标,以研究其在精子,选定的恶性肿瘤,和斯潘X-N的功能,以及在其他组织中的作用。
The sperm protein associated with nucleus in the X chromosome (SPANX) genes cluster at Xq27 in two subfamilies, SPANX-A/D and SPANX-N. SPANX-A/D is specific for hominoids and is fairly well characterized. The SPANX-N gave rise to SPANX-A/D in the hominoid lineage ∼7 MYA. Given the proposed role of SPANX genes in spermatogenesis, we have extended studies to SPANX-N gene evolution, variation, regulation of expression, and intra-sperm localization. By immunofluorescence analysis, SPANX-N proteins are localized in post-meiotic spermatids exclusively, like SPANX-A/D. But in contrast to SPANX-A/D, SPANX-N are found in all ejaculated spermatozoa rather than only in a subpopulation, are localized in the acrosome rather than in the nuclear envelope, and are expressed at a low level in several nongametogenic adult tissues as well as many cancers. Presence of a binding site for CTCF and its testis-specific paralogue BORIS in the SPANX promoters suggests, by analogy to MAGE-A1 and NY-ESO-1, that their activation in spermatogenesis is mediated by the programmed replacement of CTCF by BORIS. Based on the relative density of CpG, the more extended expression of SPANX-N compared to SPANX-A/D in nongametogenic tissues is likely attributed to differences in promoter methylation. Our findings suggest that the recent duplication of SPANX genes in hominoids was accompanied by different localization of SPANX-N proteins in post-meiotic sperm and additional expression in several nongonadal tissues. This suggests a corresponding functional diversification of SPANX gene families in hominoids. SPANX proteins thus provide unique targets to investigate their roles in the function of spermatozoa, selected malignancies, and for SPANX-N, in other tissues as well.
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