Regulation of Homeotic Genes

Several studies have identified and established the importance of the transcription factors of the homeobox gene family (HOX) in the development of human placenta [82–86]. Most HOX genes have been found stably hypo-methylated throughout gestation, suggesting that DNA methylation is not the primary mechanism involved in regulating HOX genes expression in the placenta. However, these genes show variable methylation patterns across gestation, with a general trend towards an increase in methylation over gestation. Three genes (*TLX1, HOXA10* and *DLX5*) present slightly increased methylation while their mRNA expression decreases throughout pregnancy, supporting a role for DNA methylation in their regulation [46]. Down-regulation of these genes using siRNAs specific for *DLX5*, *HOXA10* and *TLX1* in primary trophoblasts leads to loss of proliferation and to an increase in mRNA expression of di fferentiation markers, such as *ERVW-1*. This suggests that loss of these proteins is required for proper SCT development [46].
