Differential downregulation of alphaT-catenin expression in placenta: trophoblast cell type-dependent imprinting of the CTNNA3 gene.
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.
van Dijk
Marie
M
Department of Clinical Chemistry, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Mulders
Joyce
J
Könst
Andrea
A
Janssens
Barbara
B
van Roy
Frans
F
Blankenstein
Marinus
M
Oudejans
Cees
C
D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004303:Dosage Compensation, Genetic; D015536:Down-Regulation; D005260:Female; D005455:Fluorescent Antibody Technique; D018392:Genomic Imprinting; D006579:Heterozygote; D006801:Humans; D011110:Polymorphism, Genetic; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000378:metabolism*; D051178:alpha Catenin
C441963:CTNNA3 protein, human; D003598:Cytoskeletal Proteins; D051178:alpha Catenin