DREAM Mediated Regulation of GCM1 in the Human Placental Trophoblast

被引：22

作者：

Baczyk, Dora ^{[1
]}

Kibschull, Mark ^{[1
]}

Mellstrom, Britt ^{[2
]}

Levytska, Khrystyna ^{[1
]}

Rivas, Marcos ^{[2
]}

Drewlo, Sascha ^{[1
]}

Lye, Stephen J. ^{[1
,3
]}

Naranjo, Jose R. ^{[2
]}

Kingdom, John C. P. ^{[1
,3
]}

机构：

[1] Univ Toronto, Mt Sinai Hosp, Res Ctr Womens & Infants Hlth, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[2] CSIC, Natl Biotechnol Ctr, Dept Mol & Cellular Biol, Madrid, Spain

[3] Univ Toronto, Mt Sinai Hosp, Dept Obstet & Gynecol, Toronto, ON M5G 1X5, Canada

来源：

PLOS ONE | 2013年 / 8卷 / 01期

基金：

加拿大健康研究院;

关键词：

GENE-EXPRESSION; TRANSCRIPTIONAL REPRESSOR; PROTEIN; CELLS; CALSENILIN; SYNCYTIN; TERM; DIFFERENTIATION; APOPTOSIS; INTERACTS;

D O I：

10.1371/journal.pone.0051837

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The trophoblast transcription factor glial cell missing-1 (GCM1) regulates differentiation of placental cytotrophoblasts into the syncytiotrophoblast layer in contact with maternal blood. Reduced placental expression of GCM1 and abnormal syncytiotrophoblast structure are features of hypertensive disorder of pregnancy - preeclampsia. In-silico techniques identified the calcium-regulated transcriptional repressor - DREAM (Downstream Regulatory Element Antagonist Modulator) - as a candidate for GCM1 gene expression. Our objective was to determine if DREAM represses GCM1 regulated syncytiotrophoblast formation. EMSA and ChIP assays revealed a direct interaction between DREAM and the GCM1 promoter. siRNA-mediated DREAM silencing in cell culture and placental explant models significantly up-regulated GCM1 expression and reduced cytotrophoblast proliferation. DREAM calcium dependency was verified using ionomycin. Furthermore, the increased DREAM protein expression in preeclamptic placental villi was predominantly nuclear, coinciding with an overall increase in sumolylated DREAM and correlating inversely with GCM1 levels. In conclusion, our data reveal a calcium-regulated pathway whereby GCM1-directed villous trophoblast differentiation is repressed by DREAM. This pathway may be relevant to disease prevention via calcium-supplementation.

引用

页数：14

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