X-chromosome reactivation

X chromosome reactivation (XCR) is the process by which the inactive X chromosome (the Xi) is re-activated in the cells of eutherian female mammals. Therian female mammalian cells have two X chromosomes, while males have only one, requiring X-chromosome inactivation (XCI) for sex-chromosome dosage compensation. In eutherians, XCI is the random inactivation of one of the X chromosomes, silencing its expression. Much of the scientific knowledge currently known about XCR comes from research limited to mouse models or stem cells.

Partial XCR may derepress one or more genes on the Xi, and the level of restored gene expression may not be as high as it would normally be on the active X chromosome (the Xa). Complete XCR restores the Xi to Xa and erases the epigenetic memory of XCI, meaning that inducing X-inactivation again will randomly select an X chromosome to silence, rather than deterministically silencing the original Xi.[1]

XCR is an emerging topic of interest for multiple reasons:[1]

  1. Reactivating silenced genes may be a therapy for X-linked diseases in heterozygous females, such as Rett syndrome,[2] or a therapy for cancer by reactivating silenced tumor suppressor genes
  2. XCR may be a contributing factor to human disorders, such as certain cancers
  3. Understanding the mechanisms of XCR will elucidate general gene regulation principles, contributing to the study of gene silencing, epigenetic memory, and the role of long non-coding RNAs (lncRNAs)
  1. ^ a b Talon I, Janiszewski A, Chappell J, Vanheer L, Pasque V (2019). "Recent Advances in Understanding the Reversal of Gene Silencing During X Chromosome Reactivation". Frontiers in Cell and Developmental Biology. 7: 169. doi:10.3389/fcell.2019.00169. PMC 6733891. PMID 31552244.
  2. ^ Inácio P (October 2019). "New Rett Therapies May Stem From X-chromosome Reactivation Findings". Retrieved 2022-08-08.