Epigenetic and LncRNA-Mediated Regulation of X Chromosome Inactivation and Its Impact on Pathogenesis

AbstractPurpose of ReviewIn multicellular organisms, development of genetic sex determination leads to gene dosage imbalances between the sex chromosomes and the autosomes and between the sexes. In mammals with XY-based system, a dosage compensation mechanism called X chromosome inactivation (XCI) balances gene expression from unequal number of sex chromosomes between the homogametic (XX) females and heterogametic (XY) males. XCI-mediated dosage compensation involves transcriptional silencing of one of the two X chromosomes in female cells and is tightly mediated during early development.Recent FindingsThe silencing mechanism relies on coordinated action of several epigenetic mechanisms that include imprinting, long noncoding RNA (lncRNA)-mediated chromatin regulation, and nuclear organization. Alterations in the establishment and maintenance of XCI have been associated with female-specific developmental defects, X-linked diseases, and cancer.SummaryIn this review, we discuss the current understanding on the epigenetic and lncRNA-mediated regulation of XCI and how alterations in XCI are linked to developmental defects and diseases such as cancer.
Source: Current Pathobiology Reports - Category: Laboratory Medicine Source Type: research