X-CHROMOSOME INACTIVATION AND THE CONTROL OF GENE-EXPRESSION
X-CHROMOSOME INACTIVATION AND THE CONTROL OF GENE-EXPRESSION
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DOI：
10.1038/296493a0
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发表时间：
1982-01-01
期刊：
影响因子：
64.8
通讯作者：
JOHNSON, MH
中科院分区：
文献类型：
--
作者：
JOHNSON, MH
染色质的状态和基因的表达之间有什么关系？异染色质和不活跃的X染色体似乎提供了一个有吸引力的模型系统来解决这个问题，因为在X失活(或重新激活)过程中，潜在遗传活动的改变及其在许多代细胞中的遗传涉及到一大组连贯的基因的同时变化，而不是分散在基因组中的一系列基因的变化。最近在班加罗尔举行的一次会议*期间，很明显，这一假设过于简单。研究发现，X染色体的凝聚，以及基因组中其他地方的异染色质的凝聚，可能是一种次要现象，可能主要与性别的进化有关，分化过程中基因的选择性活动可能完全受到其他机制的调节。在真核哺乳动物中，胚胎开始时有两条活跃的X染色体，但父系来源的X染色体后来在滋养外胚层和初级内胚层细胞中失活(北海道大学N·高木)。这些细胞类似于成年有袋类动物中父亲的X染色体不活跃的细胞谱系(在某些谱系中是部分活跃的)，尽管尚不清楚这是由于受精时未能激活父亲的X染色体所致，还是先激活后优先失活的结果(J.Graves，拉特洛布大学)。一系列令人印象深刻的细胞遗传学、生化和胚胎学证据表明，在真核哺乳动物的初级外胚层(外胚层)中，X染色体的随机失活而不是选择性失活发生在5Y2到611Z天(Takagi；M.Monk，MRC哺乳动物发育单位，伦敦；M.Lyon，MRC放射生物学单位，Harwell)。X染色体失活，无论是随机的或父系的，以及胚胎或胚胎癌细胞(Takagi)中的X-失活，以及从干细胞群体中产生的分化细胞，导致Monk提出这两者都是由单一基因变化引起的。她提出，X基因失活可能只是更一般的遗传决定过程的一部分，这两个事件可能由相同的分子机制介导。逆转X失活的实验使这个简单但有吸引力的想法变得复杂起来。
WHAT is the relationship between the state of chromatin and the expression of genes? The heterochromatic and inactive X-chromosome appears to offer an appealing model system to tackle this question, since during X-inactivation (or reactivation) the alteration of potential genetic activity, and its inheritance through many cell generations, involves simultaneous changes to a large and coherent group of genes rather than to a series of genes scattered throughout the genome. During the course of a recent meeting in Bangalore*, it became clear that this assumption was too simple. It emerged that the condensation of the X-chromosome, and indeed of heterochromatin elsewhere in the genome, may be a secondary phenomenon, perhaps related primarily to the evolution of sex, and that the selective activity of genes during differentiation might be regulated by other mechanisms altogether. In the eutherian mammal, the embryo begins life with two active X-chromosomes, but the paternally derived one is later inactivated in trophectodermal and primary endodermal cells (N. Takagi, University of Hokkaido). The cells resemble those cell lineages in adult marsupials in which the paternal X-chromosome is inactive (it is partially active in some lineages), although it is not clear whether this is a result of failure to activate the paternal X-chromosome at fertilization, or of activation followed by preferential inactivation (J. Graves, LaTrobe University). An impressive array of cytogenetic, biochemical and embryological evidence suggests that, in the primary ectoderm (epiblast) of eutherian mammals, random rather than selective inactivation of the X-chromosome occurs between 5 Y2 and 6llz days (Takagi; M. Monk, MRC Mammalian Development Unit, London; M. Lyon, MRC Radiobiology Unit, Harwell).The simultaneous occurrence of X-inactivation, whether random or paternal and in embryo or embryonal carcinoma cell (Takagi), and the generation of differentiated cells from a stem cell population, lead Monk to propose that both arise from a single genetic change. She suggests that X-inactivation may be just one part of a more general process of genetic determination and that both events might be mediated by the same molecular mechanism. Experiments in which X-inactivation is reversed complicate this simple but attractive idea.