Differential downregulation of αT-catenin expression in placenta: Trophoblast cell type-dependent imprinting of the CTNNA3 gene

Marie van Dijk, Joyce Mulders, Andrea Könst, Barbara Janssens, Frans van Roy, Marinus Blankenstein, Cees Oudejans*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The αE-catenin is a well-known invasion suppressor. A recently described novel α-catenin, i.e. αT-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 αT-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 αT-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.

Original languageEnglish
Pages (from-to)61-65
Number of pages5
JournalGene Expression Patterns
Volume5
Issue number1
DOIs
Publication statusPublished - Nov 2004

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