Kuzmin Anastasia, Han Zhiming, Golding Michael C, Mann Mellissa R W, Latham Keith E, Varmuza Susannah
Department of Cell and Systems Biology, University of Toronto, Toronto, Ont., Canada.
Gene Expr Patterns. 2008 Jan;8(2):107-16. doi: 10.1016/j.modgep.2007.09.005. Epub 2007 Oct 9.
Genomic imprinting has dramatic effects on placental development, as has been clearly observed in interspecific hybrid, somatic cell nuclear transfer, and uniparental embryos. In fact, the earliest defects in uniparental embryos are evident first in the extraembryonic trophoblast. We performed a microarray comparison of gynogenetic and androgenetic mouse blastocysts, which are predisposed to placental pathologies, to identify imprinted genes. In addition to identifying a large number of known imprinted genes, we discovered that the Polycomb group (PcG) gene Sfmbt2 is imprinted. Sfmbt2 is expressed preferentially from the paternal allele in early embryos, and in later stage extraembryonic tissues. A CpG island spanning the transcriptional start site is differentially methylated on the maternal allele in e14.5 placenta. Sfmbt2 is located on proximal chromosome 2, in a region known to be imprinted, but for which no genes had been identified until now. This possibly identifies a new imprinted domain within the murine genome. We further demonstrate that murine SFMBT2 protein interacts with the transcription factor YY1, similar to the Drosophila PHO-RC.
基因组印记对胎盘发育具有显著影响，这在种间杂交、体细胞核移植和单亲胚胎中已得到明确观察。事实上，单亲胚胎中最早出现的缺陷首先在胚外滋养层中表现明显。我们对易患胎盘疾病的雌核发育和雄核发育小鼠囊胚进行了微阵列比较，以鉴定印记基因。除了鉴定出大量已知的印记基因外，我们还发现多梳蛋白家族（PcG）基因Sfmbt2是印记基因。Sfmbt2在早期胚胎以及后期胚外组织中优先从父本等位基因表达。在e14.5胎盘的母本等位基因上，跨越转录起始位点的一个CpG岛存在差异甲基化。Sfmbt2位于近端2号染色体上一个已知为印记区域，但此前尚未鉴定出该区域的基因。这可能确定了小鼠基因组内一个新的印记结构域。我们进一步证明，小鼠SFMBT2蛋白与转录因子YY1相互作用，类似于果蝇PHO-RC。
