van Dijk Marie, Mulders Joyce, Könst Andrea, Janssens Barbara, van Roy Frans, Blankenstein Marinus, Oudejans Cees
Department of Clinical Chemistry, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Gene Expr Patterns. 2004 Nov;5(1):61-5. doi: 10.1016/j.modgep.2004.06.006.
The alphaE-catenin is a well-known invasion suppressor. A recently described novel alpha-catenin, i.e. alphaT-catenin (CTNNA3), shows related functions being necessary for the formation of cell-cell adhesion complexes. We recently demonstrated that the 10q21.3 region containing the CTNNA3 gene shows a parent-of-origin effect and that transcription of the CTNNA3 gene is downregulated in placental tissues of complete androgenetic origin. As this suggests that the CTNNA3 gene is subject to imprinting, we performed allele-specific RT-PCR on early placenta tissues using informative heterozygous samples. This was supplemented by immunostaining for alphaT-catenin, p57KIP2 and low molecular weight cytokeratin in tissues of a partial hydatidiform mole. As shown here we demonstrate that the CTNNA3 gene is subject to imprinting with preferential expression of the maternal allele in first trimester placental tissues. Imprinting, however, is trophoblast cell type-dependent: expression in extravillus trophoblast is biallelic; expression in villus cytotrophoblast is from the maternal allele only. Expression of alphaT-catenin is lost in villus syncytiotrophoblast as well as in extravillus trophoblast following epithelial-mesenchymal transition. The trophoblast cell type-dependent imprinting of CTNNA3 is identical to p57KIP2 imprinting with respect to trophoblast cell type (villus) and parental origin of the expressed allele (maternal). This suggests that gene dosage compensation of CTNNA3 and p57KIP2 in the placenta shares a conserved regulatory mechanism that correlates with an early step in trophoblast determination, i.e. differentiation into villus or extravillus trophoblast.
αE-连环蛋白是一种著名的侵袭抑制因子。最近描述的一种新型α-连环蛋白，即αT-连环蛋白（CTNNA3），显示出对于细胞间粘附复合物形成所必需的相关功能。我们最近证明，包含CTNNA3基因的10q21.3区域呈现亲本来源效应，并且CTNNA3基因的转录在完全雄激素来源的胎盘组织中下调。由于这表明CTNNA3基因受到印记调控，我们使用信息性杂合样本对早期胎盘组织进行了等位基因特异性逆转录聚合酶链反应（RT-PCR）。这通过对部分葡萄胎组织中的αT-连环蛋白、p57KIP2和低分子量细胞角蛋白进行免疫染色得到补充。如本文所示，我们证明CTNNA3基因受到印记调控，在孕早期胎盘组织中母本等位基因优先表达。然而，印记是滋养层细胞类型依赖性的：在绒毛外滋养层中的表达是双等位基因的；在绒毛细胞滋养层中的表达仅来自母本等位基因。在上皮-间充质转化后，αT-连环蛋白的表达在绒毛合体滋养层以及绒毛外滋养层中丢失。CTNNA3的滋养层细胞类型依赖性印记在滋养层细胞类型（绒毛）和表达等位基因的亲本来源（母本）方面与p57KIP2印记相同。这表明胎盘组织中CTNNA3和p57KIP2的基因剂量补偿共享一种保守的调控机制，该机制与滋养层细胞决定的早期步骤相关，即分化为绒毛或绒毛外滋养层。
