X-inactive-specific transcript: a long noncoding RNA with a complex role in sex differences in human disease.

Area of Science:

• Genetics
• Epigenetics
• Human Biology

Background:

• The X and Y chromosomes determine biological sex (XX for females, XY for males).
• Long noncoding RNA XIST is crucial for X chromosome inactivation (XCI) in females, balancing X-linked gene expression.
• XIST was initially thought to be female-specific but is now detected in male cells, influencing disease development.

Purpose of the Study:

• To review current knowledge on XIST structure, function, and its role in human diseases.
• To focus on the abnormal expression of XIST in males and its contribution to sex-biased diseases.
• To highlight how XIST may explain sex differences in disease penetrance, presentation, and progression.

Main Methods:

• Literature review of XIST's role in gene regulation (epigenetic, chromatin remodeling, transcriptional, translational).
• Analysis of XIST's abnormal expression in sexually dimorphic diseases like cancers, autoimmune, and neurological disorders.
• Examination of XCI escape and skewed XCI in relation to disease severity and sex bias.

Main Results:

• XIST expression in males is linked to sex-biased disease conditions, similar to females.
• Individuals with supernumerary X chromosomes (e.g., Klinefelter syndrome) show increased predisposition to female-biased diseases.
• X chromosome content, particularly two X chromosomes, is associated with increased longevity.

Conclusions:

• Abnormal XIST expression and function in males contribute to sex differences in human health and disease.
• Understanding XIST's mechanisms in sex-biased diseases can lead to personalized and sex-specific medical treatments.
• Further research into XIST's molecular role is essential for improving patient diagnosis and therapy.