Disease relevance of GCM1

• GCM1 expression has been shown to affect placental branching and vasculogenesis, abnormalities of which may result in the development of pre-eclampsia [1].
• Our results suggest that GCM1 is a distinct transcription factor involved in placental disease and altered expression of the GCM1 gene may contribute to the etiology of pre-eclampsia [1].
• Using G-free reporter constructs carrying multiple copies of wild-type or mutant GCMa-binding site (GBS) in front of a synthetic TATA box, we observed specific transcriptional activities of recombinant hGCMa/1 proteins prepared from a baculovirus--insect cell or Escherichia coli expression system [2].

High impact information on GCM1

• We show that hFBW2 interacts with hGCMa in a phosphorylation-dependent manner and promotes hGCMa ubiquitination [3].
• A GCM motif protein is involved in placenta-specific expression of human aromatase gene [4].
• We conclude that the normal human thymus does not express GCMA or PTH, and therefore, in contrast to the mouse, the human thymus is not a source of PTH production [5].
• GCMA and GCMB are related transcription factors that are critically important for embryological development of the placenta and parathyroid glands, respectively [5].
• Decreased placental GCM1 (glial cells missing) gene expression in pre-eclampsia [1].

Biological context of GCM1

• Of 36 placentae without pre-eclampsia (ranged from 5-40 weeks of gestation), the level of GCM1 expression was relatively constant before late third trimester [1].
• Genomic organization, chromosomal localization, and the complete 22 kb DNA sequence of the human GCMa/GCM1, a placenta-specific transcription factor gene [6].
• In this study immunohistochemistry, Western blot, and quantitative real-time PCR were used to investigate GCM1 expression at different gestational ages and in pre-eclampsia [1].
• Using G-free reporter constructs containing the native syncytin promoter, a TATA box downstream of the proximal GBS in the syncytin promoter was shown to be essential for the transcription activation directed by hGCMa/1 [2].

Anatomical context of GCM1

• Complex patterns of GCM1 mRNA and protein in villous and extravillous trophoblast cells of the human placenta [7].
• The mammalian homologue of the glial cells missing (GCM) gene, GCM1, is selectively expressed in the placenta [1].
• By contrast to mouse thymus, analysis of 22 samples of human thymus tissue by RT-PCR and/or immunohistochemistry failed to demonstrate the expression of either PTH or GCMA [5].
• In contrast, TGF-beta induced the expression of a marker of differentiated labyrinthine trophoblasts, Gcm1, only in the SM10 cell line [8].

Other interactions of GCM1

• Median concentrations of PLAC1 and GCM1 mRNA in plasma of pre-eclamptic subjects respectively were 1625 and 2141 copies/ml, significantly higher than 195 and 881 copies/ml, the values for controls (Mann-Whitney test, p<0.001) [9].

Analytical, diagnostic and therapeutic context of GCM1

• In situ hybridization studies showed that the GCM1 mRNA was expressed in villous cytotrophoblast cells, but only a subset and never within cells immediately at the base of columns [7].

References