Random X inactivation and extensive mosaicism in human placenta revealed by analysis of allele-specific gene expression along the X chromosome

• Published in: PloS one 2010-06, Vol.5 (6), p.e10947-e10947
• Main Authors: Moreira de Mello, Joana Carvalho, de Araújo, Erica Sara Souza, Stabellini, Raquel, Fraga, Ana Maria, de Souza, Jorge Estefano Santana, Sumita, Denilce R, Camargo, Anamaria A, Pereira, Lygia V
• Format: Article
• Language: English
• Subjects: Alleles; Analysis; Animal tissues; Automation; Biological evolution; Chromosomes; Chromosomes, Human, X; Compensation; Deactivation; Deoxyribonucleic acid; DNA; Dosage; Dosage compensation; Epigenetics; Evolution (Biology); Evolutionary biology; Evolutionary Biology/Human Evolution; Female; Females; Fibroblasts; Gene Expression; Gene silencing; Genes; Genetic aspects; Genetic engineering; Genetic testing; Genetics and Genomics/Epigenetics; Genetics and Genomics/Gene Expression; Genomes; Genomic Imprinting; Human performance; Humans; Inactivation; Male; Males; Mammals; Medical research; Mosaicism; Placenta; Placenta - metabolism; Polymorphism, Single Nucleotide; Pregnancy; Single-nucleotide polymorphism; Stem cells; X Chromosome Inactivation; X Chromosomes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0010947

Imprinted inactivation of the paternal X chromosome in marsupials is the primordial mechanism of dosage compensation for X-linked genes between females and males in Therians. In Eutherian mammals, X chromosome inactivation (XCI) evolved into a random process in cells from the embryo proper, where either the maternal or paternal X can be inactivated. However, species like mouse and bovine maintained imprinted XCI exclusively in extraembryonic tissues. The existence of imprinted XCI in humans remains controversial, with studies based on the analyses of only one or two X-linked genes in different extraembryonic tissues. Here we readdress this issue in human term placenta by performing a robust analysis of allele-specific expression of 22 X-linked genes, including XIST, using 27 SNPs in transcribed regions. We show that XCI is random in human placenta, and that this organ is arranged in relatively large patches of cells with either maternal or paternal inactive X. In addition, this analysis indicated heterogeneous maintenance of gene silencing along the inactive X, which combined with the extensive mosaicism found in placenta, can explain the lack of agreement among previous studies. Our results illustrate the differences of XCI mechanism between humans and mice, and highlight the importance of addressing the issue of imprinted XCI in other species in order to understand the evolution of dosage compensation in placental mammals.