Global analysis of X-chromosome dosage compensation.
Global analysis of X-chromosome dosage compensation.
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DOI：
10.1186/jbiol30
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发表时间：
2006
影响因子：
--
通讯作者：
Oliver B
中科院分区：
文献类型：
--
作者：
Gupta V;Parisi M;Sturgill D;Nuttall R;Doctolero M;Dudko OK;Malley JD;Eastman PS;Oliver B
雌性果蝇有两条X染色体和两组常染色体(XX；AA)，而雄性只有一条X染色体和两组常染色体(X；AA)。果蝇雄性体细胞通过部署雄性特异性致死(MSL)复合体来补偿X染色体的单一副本，MSL复合体增加了X染色体的转录。雄性生殖细胞缺乏MSL复合体，说明生殖系X染色体剂量补偿不依赖于MSL，或者生殖细胞不进行剂量补偿。为了研究生殖细胞是否存在剂量补偿，我们使用DNA微阵列直接检测了X染色体转录本，并在XX；AA和X；AA生殖系组织中显示了相同的表达。在X；AA生殖细胞中，单个X染色体的表达大约是单个常染色体的两倍。这一机制确保了X染色体在两性之间的平衡表达，更重要的是，它确保了单个X染色体和常染色体组之间的平衡表达。奇怪的是，雌性哺乳动物体内X染色体的失活降低了X染色体的有效剂量，这意味着女性面临着与男性相同的X染色体转录本缺陷。与大多数目前的剂量补偿模型相反，我们还发现在秀丽线虫和小鼠的X；AA和XX；AA体细胞中X染色体的表达增加。果蝇的生殖细胞弥补了X染色体的剂量。这是通过平衡X染色体和常染色体在X；AA细胞中的表达而发生的。X染色体在X；AA个体中的表达增加似乎是系统发育保守的。
Drosophila melanogaster females have two X chromosomes and two autosome sets (XX;AA), while males have a single X chromosome and two autosome sets (X;AA). Drosophila male somatic cells compensate for a single copy of the X chromosome by deploying male-specific-lethal (MSL) complexes that increase transcription from the X chromosome. Male germ cells lack MSL complexes, indicating that either germline X-chromosome dosage compensation is MSL-independent, or that germ cells do not carry out dosage compensation. To investigate whether dosage compensation occurs in germ cells, we directly assayed X-chromosome transcripts using DNA microarrays and show equivalent expression in XX;AA and X;AA germline tissues. In X;AA germ cells, expression from the single X chromosome is about twice that of a single autosome. This mechanism ensures balanced X-chromosome expression between the sexes and, more importantly, it ensures balanced expression between the single X chromosome and the autosome set. Oddly, the inactivation of an X chromosome in mammalian females reduces the effective X-chromosome dose and means that females face the same X-chromosome transcript deficiency as males. Contrary to most current dosage-compensation models, we also show increased X-chromosome expression in X;AA and XX;AA somatic cells of Caenorhabditis elegans and mice. Drosophila germ cells compensate for X-chromosome dose. This occurs by equilibrating X-chromosome and autosome expression in X;AA cells. Increased expression of the X chromosome in X;AA individuals appears to be phylogenetically conserved.