MAOA and GYG2 are submitted to X chromosome inactivation in human fibroblasts

Abstract

X chromosome inactivation (XCI) is a comprehensively studied phenomenon that helped to highlight the heritable nature of epigenetic modifications. Although it consists of the transcriptional inactivation of a whole X chromosome in females, some genes escape this process and present bi-allelic expression. Using human fibroblasts with skewed inactivation, we determined allele-specific expression of two X-linked genes previously described to escape XCI in rodent/human somatic cell hybrids, MAOA and GYG2, and the pattern of DNA methylation of their 5' end. Results from these complementary methodologies let us to conclude that both genes are subjected to X inactivation in normal human fibroblasts, indicating that hybrid cells are not an adequate system for studying epigenotypes. We emphasize the need of an analysis of XCI in normal human cell lines, helping us to determine more precisely which X-linked genes contribute to differences among genders and to the phenotypes associated with sex chromosomes aneuploidies.

Meta‐analysis argues for a female‐specific role of MAOA‐uVNTR in panic disorder in four European populations

“…As MAOA is localized on the X-chromosome, it may be subjected to X-chromosomal inactivation. Indeed MAOA undergoes Xchromosomal inactivation in human fibroblasts, although this alternatively has been attributed to cis-acting elements in human brain tissue [Nordquist and Oreland, 2006;Pinsonneault et al, 2006;Stabellini et al, 2009]. Thus, it remains to be resolved whether MAOA escapes from or is subject to X-inactivation.…”

Characterization of allele-specific expression of the X-linked gene MAO-A in trophectoderm cells of bovine embryos produced by somatic cell nuclear transfer

“…We have previously described the allele-specific expression pattern in bovine embryos produced in vitro from the 4-cell stage to the expanded blastocyst stage (Ferreira et al, 2010) for MAO-A, which is subject to XCI (Benjamin et al, 2000, Xue et al, 2002Stabellini et al, 2009). In that study, we detected only the maternal allele at the morula stage, and both alleles were detected at the expanded blastocyst stage.…”

“…genes located on this chromosome are known to escape the inactivation process (Berletch et al, 2015), unlike MAO-A, which is subject to XCI (Benjamin et al, 2000;Xue et al, 2002;Stabellini et al, 2009). Yang et al (2007) commented that XCI can be aberrantly established in cloned embryos due to imprinting pattern alterations in the placenta.…”

“…These genes are actively expressed in the context of silenced chromatin (Boggs et al, 2002) and have an important role in determining sex differences (Heard and Disteche, 2006;Berletch et al, 2015). The gene monoamine oxidase type A (MAO-A) is located on the X chromosome, and is subject to XCI (Benjamin et al, 2000;Xue et al, 2002;Stabellini et al, 2009). Xue et al (2002) demonstrated random mono-allelic expression of MAO-A, confirming that this gene is subject to XCI in cattle.…”

Triagem funcional de genes envolvidos no processo de manutenção da inativação do cromossomo X em humanos

“…Normalmente, quando o gene HPRT mutado está localizado no cromossomo X ativo e o gene selvagem no X inativo, as células são capazes de sobreviver em meio de cultura contendo 6TG ou 8AZAG, mas são incapazes de sobreviver em meio HAT. Se ocorrer indução da reativação do cromossomo X, tais células tornam-se capazes de sobreviver em meio HAT (e incapazes de sobreviver em meio contendo 6TG ou 8AZAG), permitindo a seleção da população de células na qual esse locus do cromossomo X foi reativado com sucesso (Figura 8) (Migeon, 1970;Vasques & Pereira, 2001;Stabellini et al, 2009;Mekhoubad et al, 2012).…”