Identification of an imprinted gene cluster in the X-inactivation center.
Identification of an imprinted gene cluster in the X-inactivation center.
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DOI：
10.1371/journal.pone.0071222
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ishino F
中科院分区：
文献类型：
--
作者：
Kobayashi S;Totoki Y;Soma M;Matsumoto K;Fujihara Y;Toyoda A;Sakaki Y;Okabe M;Ishino F
哺乳动物的发育受到称为基因组印记的表观遗传现象的强烈影响，其中印记基因的父或母等位基因被表达。父源性表达的Xist基因是一种印迹基因，被认为是一种单一的顺式作用因子，在植入前小鼠胚胎中抑制父源性遗传的X染色体。这意味着X染色体失活也需要在非常早期的发育阶段进行基因印迹。然而，印迹X染色体失活的确切机制仍然未知，并且关于X染色体上印迹基因的信息很少。在这项研究中，我们研究了是否有其他印记基因比Xist表达的非活性的父亲X染色体和表达的女性胚胎在植入前阶段。我们专注于小RNA，并通过用绿色荧光蛋白标记女性X染色体来比较它们在性别之间的表达模式。因此，我们鉴定了两个微（mi）RNA-miR-374- 5 p和miR-421- 3 p-定位在Xist附近，其主要在雌性囊胚中表达。等位基因表达分析显示，这些miRNA确实是从Xp印迹和表达的。进一步分析相邻位点的印迹状态，发现从Xp表达的一大簇印迹基因：Jpx，Ftx和Zcchc 13。据我们所知，这是第一个确定集群的印记基因的顺式作用的调控区称为X-失活中心。这一发现可能有助于理解在早期哺乳动物发育过程中调节印记X染色体失活的分子机制。
Mammalian development is strongly influenced by the epigenetic phenomenon called genomic imprinting, in which either the paternal or the maternal allele of imprinted genes is expressed. Paternally expressed Xist, an imprinted gene, has been considered as a single cis-acting factor to inactivate the paternally inherited X chromosome (Xp) in preimplantation mouse embryos. This means that X-chromosome inactivation also entails gene imprinting at a very early developmental stage. However, the precise mechanism of imprinted X-chromosome inactivation remains unknown and there is little information about imprinted genes on X chromosomes. In this study, we examined whether there are other imprinted genes than Xist expressed from the inactive paternal X chromosome and expressed in female embryos at the preimplantation stage. We focused on small RNAs and compared their expression patterns between sexes by tagging the female X chromosome with green fluorescent protein. As a result, we identified two micro (mi)RNAs–miR-374-5p and miR-421-3p–mapped adjacent to Xist that were predominantly expressed in female blastocysts. Allelic expression analysis revealed that these miRNAs were indeed imprinted and expressed from the Xp. Further analysis of the imprinting status of adjacent locus led to the discovery of a large cluster of imprinted genes expressed from the Xp: Jpx, Ftx and Zcchc13. To our knowledge, this is the first identified cluster of imprinted genes in the cis-acting regulatory region termed the X-inactivation center. This finding may help in understanding the molecular mechanisms regulating imprinted X-chromosome inactivation during early mammalian development.
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影响因子：
4.5
作者：
Kobayashi H;Sakurai T;Imai M;Takahashi N;Fukuda A;Yayoi O;Sato S;Nakabayashi K;Hata K;Sotomaru Y;Suzuki Y;Kono T
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