Incomplete X chromosome dosage compensation in chorionic villi of human placenta

Abstract

Studies of glucose-6-phosphate dehydrogenase (G6PD) in heterozygous cells from chorionic villi of five fetal and one newborn placenta show that the locus on the allocyclic X is expressed in many cells of this trophectoderm derivative. Heterodimers were present in clonal populations of cells with normal diploid karyotype and a late replicating X chromosome. The expression of the two X chromosomes was unequal, based on ratios of homodimers and heterodimers in clones. Studies of DNA, digested with Hpa II and probed with cloned genomic G6PD sequences, indicate that expression of the locus in chorionic villi is associated with hypomethylation of 3' CpG clusters. These findings suggest that dosage compensation, at least at the G6PD locus, has not been well established or maintained (or both) in placental tissue. Furthermore, the active X chromosome in these human cells of trophoblastic origin can be either the paternal or maternal one; therefore, paternal X inactivation in extraembryonic lineages is not an essential feature of mammalian X dosage compensation.