Paternal RLIM/Rnf12 is a survival factor for milk-producing alveolar cells.
Paternal RLIM/Rnf12 is a survival factor for milk-producing alveolar cells.
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DOI：
10.1016/j.cell.2012.02.056
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发表时间：
2012-04-27
期刊：
影响因子：
64.5
通讯作者：
Bach I
中科院分区：
文献类型：
--
作者：
Jiao B;Ma H;Shokhirev MN;Drung A;Yang Q;Shin J;Lu S;Byron M;Kalantry S;Mercurio AM;Lawrence JB;Hoffmann A;Bach I
在雌性小鼠胚胎中，体细胞会经历一种随机形式的X染色体失活（XCI），而胎盘中的胚外滋养层细胞则会经历印记X染色体失活，仅使父本的X染色体沉默。印记X染色体失活的起始需要X连锁基因Rnf12的有功能的母本等位基因，该基因编码泛素连接酶Rnf12/RLIM。在此我们发现，雌性乳腺中Rnf12基因敲除（KO）会抑制怀孕时的腺泡分化和乳汁生成。缺乏Rnf12/RLIM的腺泡细胞一旦从乳腺上皮细胞分化出来就会发生凋亡。遗传学分析表明，这些功能主要由父本的Rnf12等位基因介导，这是因为乳腺上皮细胞中的非随机X染色体失活主要使母本的X染色体沉默。这些结果确定父本的Rnf12/RLIM是产乳腺泡细胞的关键存活因子，并为乳腺上皮细胞中与胚外滋养层细胞中所发现的相反的印记X染色体失活模式提供了有力证据。
In female mouse embryos, somatic cells undergo a random form of X chromosome inactivation (XCI), while extraembryonic trophoblast cells in the placenta undergo imprinted XCI, silencing exclusively the paternal X chromosome. Initiation of imprinted XCI requires a functional maternal allele of the X-linked gene Rnf12 which encodes the ubiquitin ligase Rnf12/RLIM. Here we find that knockout (KO) of Rnf12 in female mammary glands inhibits alveolar differentiation and milk production upon pregnancy. Alveolar cells lacking Rnf12/RLIM undergo apoptosis as soon as they differentiate from mammary epithelia. Genetic analyses demonstrate that these functions are mediated primarily by the paternal Rnf12 allele due to non-random XCI in mammary epithelial cells which primarily silence their maternal X chromosomes. These results identify paternal Rnf12/RLIM as a critical survival factor for milk-producing alveolar cells and provide strong evidence for an imprinted XCI pattern in mammary epithelial cells opposite to that found in extraembryonic trophoblast cells.
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DOI：
10.1073/pnas.0807640106
发表时间：
2009-03-24
影响因子：
11.1
作者：
Li, Wenjing;Ferguson, Brian J.;Watson, Christine J.
通讯作者：
Watson, Christine J.
影响因子：
1.6
作者：
Mohanty, Ashok K.;Fisher, Andrew J.;Kaushik, Jai K.
通讯作者：
Kaushik, Jai K.
影响因子：
3.2
作者：
Gown, AM;Willingham, MC
通讯作者：
Willingham, MC
影响因子：
56.9
作者：
Gregg, Christopher;Zhang, Jiangwen;Dulac, Catherine
通讯作者：
Dulac, Catherine
影响因子：
21.3
作者：
Asselin-Labat, Marie-Liesse;Sutherland, Kate D.;Visvader, Jane E.
通讯作者：
Visvader, Jane E.