Shevchenko Alexander I, Zakharova Irina S, Elisaphenko Eugeny A, Kolesnikov Nicolay N, Whitehead Siobhan, Bird Christine, Ross Mark, Weidman Jennifer R, Jirtle Randy L, Karamysheva Tatiana V, Rubtsov Nicolay B, VandeBerg John L, Mazurok Nina A, Nesterova Tatyana B, Brockdorff Neil, Zakian Suren M
Institute of Cytology and Genetics, Russian Academy of Sciences, Siberian Department, Novosibirsk, Russia.
Chromosome Res. 2007;15(2):127-36. doi: 10.1007/s10577-006-1115-9. Epub 2007 Mar 5.
X inactivation, the transcriptional silencing of one of the two X chromosomes in female mammals, achieves dosage compensation of X-linked genes relative to XY males. In eutherian mammals X inactivation is regulated by the X-inactive specific transcript (Xist), a cis-acting non-coding RNA that triggers silencing of the chromosome from which it is transcribed. Marsupial mammals also undergo X inactivation but the mechanism is relatively poorly understood. We set out to analyse the X chromosome in Monodelphis domestica and Didelphis virginiana, focusing on characterizing the interval defined by the Chic1 and Slc16a2 genes that in eutherians flank the Xist locus. The synteny of this region is retained on chicken chromosome 4 where other loci belonging to the evolutionarily ancient stratum of the human X chromosome, the so-called X conserved region (XCR), are also located. We show that in both M. domestica and D. virginiana an evolutionary breakpoint has separated the Chic1 and Slc16a2 loci. Detailed analysis of opossum genomic sequences revealed linkage of Chic1 with the Lnx3 gene, recently proposed to be the evolutionary precursor of Xist, and Fip1, the evolutionary precursor of Tsx, a gene located immediately downstream of Xist in eutherians. We discuss these findings in relation to the evolution of Xist and X inactivation in mammals.
X染色体失活是雌性哺乳动物两条X染色体之一的转录沉默过程，它实现了相对于XY雄性个体X连锁基因的剂量补偿。在真兽类哺乳动物中，X染色体失活受X染色体失活特异性转录本（Xist）调控，Xist是一种顺式作用非编码RNA，可触发其转录所在染色体的沉默。有袋类哺乳动物也会发生X染色体失活，但其机制相对了解较少。我们着手分析家短尾负鼠和弗吉尼亚负鼠的X染色体，重点是对Chic1和Slc16a2基因所界定的区间进行特征描述，在真兽类动物中这两个基因位于Xist基因座两侧。该区域的同线性在鸡的4号染色体上得以保留，人类X染色体进化上古老层级的其他基因座，即所谓的X保守区域（XCR）也位于此。我们发现，在家短尾负鼠和弗吉尼亚负鼠中，一个进化断点将Chic1和Slc16a2基因座分开。对负鼠基因组序列的详细分析揭示了Chic1与Lnx3基因的连锁关系，Lnx3最近被认为是Xist的进化前体，以及与Fip1的连锁关系，Fip1是Tsx的进化前体，在真兽类动物中Tsx是位于Xist紧邻下游的一个基因。我们结合Xist和哺乳动物X染色体失活的进化来讨论这些发现。
