Up to Date Discoveries of X Chromosome Inactivation in Humans Leading to Prospective Treatments for Chromosome-linked Disorders

Abstract

Mammalian dosage compensation is a complex mechanism allowing inactivation of single X chromosome of the female to compensate to that of the X chromosome of the male. The mechanism includes many long non-coding RNA; mainly XIST, a noncoding RNA which coats the X chromosome to be inactivated and TSIX, another noncoding RNA act as a negative regulator of XIST preventing inactivation of the second X chromosome. Both XIST and TSIX and several other transcription factors along with polycomb proteins (PRC) work together in controlling the inactivation of one X chromosome while the other X chromosome remains active. This is facilitated by the sensing mechanism called the n-1 theory, induced by the X pairing region (XPR) allowing X chromosome pairing before inactivation. X inactivation occurs randomly and begins at the late blastocyst stage of an embryo when the cells start to differentiate by losing pluripotency. Therefore, pluripotent factors play an important role in inducing X chromosome inactivation. Once X chromosome is inactivated it is passed along cell division and maintained throughout life. This review discusses up-to-date discovered pathways involved in mammalian dosage compensation, from initiation to maintenance of the X chromosome inactivation and potential therapeutic effects for X chromosome-linked disorders.