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

Purpose of Review: In 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 Findings: The 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. Summary: In 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.

Duke Scholars

Author Eda Yildirim Cell Biology