為確保雌性動(dòng)物不會(huì)有多余的X-染色體基因產(chǎn)物,,每個(gè)細(xì)胞中兩個(gè)X-染色體中的一個(gè)會(huì)被抑制,。在胚胎生成過(guò)程中,這個(gè)X-染色體失活(XCI)過(guò)程的有印記形式,,會(huì)在胚胎發(fā)育過(guò)程大約“四細(xì)胞階段”在檢測(cè)出父方X-染色體(Xp)上有Xist RNA的表達(dá)之后選擇性地將父方X-染色體抑制,。之后,XCI的一種胚胎形式會(huì)出現(xiàn)在胚胎本身的發(fā)育中的胚泡中,,隨機(jī)地使父方或母方X-染色體失去活性,。
Shin等人利用小鼠的遺傳研究結(jié)果發(fā)現(xiàn),“Rnf12/RLIM泛素連接酶”的母方沉積在最初過(guò)程的啟動(dòng)中,、而不是在之后的隨機(jī)X-染色體抑制中起關(guān)鍵作用,。(生物谷Bioon.com)
生物谷推薦英文摘要:
Nature doi:10.1038/nature09457
Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice
JongDae Shin,Michael Bossenz,Young Chung,Hong Ma,Meg Byron,Naoko Taniguchi-Ishigaki,Xiaochun Zhu,Baowei Jiao,Lisa L. Hall,Michael R. Green,Stephen N. Jones,Irm Hermans-Borgmeyer,Jeanne B. Lawrence& Ingolf Bach
Two forms of X-chromosome inactivation (XCI) ensure the selective silencing of female sex chromosomes during mouse embryogenesis. Imprinted XCI begins with the detection of Xist RNA expression on the paternal X?chromosome (Xp) at about the four-cell stage of embryonic development. In the embryonic tissues of the inner cell mass, a random form of XCI occurs in blastocysts that inactivates either Xp or the maternal X?chromosome (Xm)1, 2. Both forms of XCI require the non-coding Xist RNA that coats the inactive X?chromosome from which it is expressed. Xist has crucial functions in the silencing of X-linked genes, including Rnf12 (refs 3, 4) encoding the ubiquitin ligase RLIM (RING finger LIM-domain-interacting protein). Here we show, by targeting a conditional knockout of Rnf12 to oocytes where RLIM accumulates to high levels, that the maternal transmission of the mutant X?chromosome (Δm) leads to lethality in female embryos as a result of defective imprinted XCI. We provide evidence that in Δm female embryos the initial formation of Xist clouds and Xp silencing are inhibited. In contrast, embryonic stem cells lacking RLIM are able to form Xist clouds and silence at least some X-linked genes during random XCI. These results assign crucial functions to the maternal deposit of Rnf12/RLIM for the initiation of imprinted XCI.