THE SEX-DETERMINING REGION OF THE HUMAN Y-CHROMOSOME ENCODES A FINGER PROTEIN
THE SEX-DETERMINING REGION OF THE HUMAN Y-CHROMOSOME ENCODES A FINGER PROTEIN
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DOI：
10.1016/0092-8674(87)90595-2
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发表时间：
1987-12-24
期刊：
影响因子：
64.5
通讯作者：
BROWN, LG
中科院分区：
文献类型：
--
作者：
PAGE, DC;MOSHER, R;BROWN, LG
Y染色体的存在与否决定了哺乳动物胚胎发育为雄性还是雌性。在人类中，对“性别逆转”个体的基因缺失分析发现，Y染色体的一小部分是诱导双势性腺的睾丸分化所必需和充分的。我们报道了人类Y染色体上含有部分或全部睾丸决定位点的230千碱基片段的克隆。该克隆区域跨越了携带y染色体160千碱基的女性的缺失区域，该区域内的某些DNA序列在进化过程中高度保守；在小鼠Y染色体的性别决定区域内发现了同源序列。人类Y染色体上这一保守DNA的核苷酸序列表明，它编码一种具有多个“手指”结构域的蛋白质，这在青蛙转录因子IIIA中首次被描述。编码蛋白可能以序列特异性的方式与核酸结合，并可能调节转录。人类和其他哺乳动物的X染色体上有非常相似的DNA序列。我们讨论了y编码手指蛋白是睾丸决定因素的可能性，并提出了性别决定模型，以适应X染色体上相关位点的发现。鸟类中类似序列的存在表明，它不仅可能在哺乳动物的XX/XY性别决定系统中起作用，而且可能在鸟类的ZZ/ZW系统中起作用。
The presence or absence of the Y chromosome determines whether a mammalian embryo develops as a male or female. In humans, genetic deletion analysis of "sex-reversed" individuals has identified a small portion of the Y chromosome necessary and sufficient to induce testicular differentiation of the bipotential gonad. We report the cloning of a 230-kilobase segment of the human Y chromosome that contains some or all of the testis-determining locus. The cloned region spans the deletion in a female who carries all but 160 kilobases of the Y. Certain DNA sequences within this region were highly conserved during evolution; homologous sequences are found within the sex-determining region of the mouse Y chromosome. The nucleotide sequence of this conserved DNA on the human Y chromosome suggests that it encodes a protein with multiple "finger" domains, as first described in frog transcription factor IIIA. The encoded protein probably binds to nucleic acids in a sequence-specific manner, and may regulate transcription. Very similar DNA sequences occur on the X chromosome of humans and other mammals. We discuss the possibility that the Y-encoded finger protein is the testis-determining factor, and propose models of sex determination accomodating the finding of a related locus on the X chromosome. The presence of similar sequences in birds suggests a possible role not only in the XX/XY sex determination system of mammals, but also in the ZZ/ZW system of birds.