Lee Jeannie T
Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Curr Biol. 2003 Mar 18;13(6):R242-54. doi: 10.1016/s0960-9822(03)00162-3.
In classical Mendelian inheritance, each parent donates a set of chromosomes to its offspring so that maternally and paternally encoded information is expressed equally. The phenomena of X-chromosome inactivation (XCI) and autosomal imprinting in mammals violate this dogma of genetic equality. In XCI, one of the two female X chromosomes is silenced to equalize X-linked gene dosage between XX and XY individuals. In genomic imprinting, parental marks determine which of the embryo's two autosomal alleles will be expressed. Although XCI and imprinting appear distinct, molecular evidence now shows that they share a surprising number of features. Among them are cis-acting control centers, long-distance regulation and differential DNA methylation. Perhaps one of the most intriguing similarities between XCI and imprinting has been their association with noncoding and antisense RNAs. Very recent data also suggest the common involvement of histone modifications and chromatin-associated factors such as CTCF. Collectively, the evidence suggests that XCI and genomic imprinting may have a common origin. Here, I hypothesize that the need for X-linked dosage compensation was a major driving force in the evolution of genomic imprinting in mammals. I propose that imprinting was first fixed on the X chromosome for XCI and subsequently acquired by autosomes.
在经典的孟德尔遗传中，每个亲本向其后代捐赠一组染色体，以便母本和父本编码的信息能够平等表达。哺乳动物中的X染色体失活（XCI）和常染色体印记现象违背了这种基因平等的教条。在XCI中，两条雌性X染色体中的一条会沉默，以使XX和XY个体之间的X连锁基因剂量相等。在基因组印记中，亲本印记决定胚胎的两个常染色体等位基因中哪一个会被表达。尽管XCI和印记看起来不同，但分子证据现在表明它们有惊人数量的共同特征。其中包括顺式作用控制中心、远距离调控和DNA甲基化差异。也许XCI和印记之间最有趣的相似之处之一是它们与非编码RNA和反义RNA的关联。最近的数据还表明组蛋白修饰和染色质相关因子（如CTCF）也共同参与其中。总体而言，证据表明XCI和基因组印记可能有共同的起源。在此，我假设对X连锁剂量补偿的需求是哺乳动物基因组印记进化的主要驱动力。我提出印记首先在X染色体上固定用于XCI，随后被常染色体获得。
