From the Guidelines
X chromosome inactivation is a crucial mechanism that ensures dosage compensation between males and females by silencing one of the two X chromosomes in female cells, resulting in the formation of a Barr body, with the number of Barr bodies corresponding to the number of X chromosomes minus one. This process is essential for preventing developmental abnormalities and is influenced by various factors, including the X-inactivation center (XIC) and the XIST gene, which produces a non-coding RNA that coats the chromosome to be inactivated 1. The inactivation of one X chromosome makes the female heart a mosaic of two different cardiomyocytes, one with the maternal X chromosome and one with the paternal X chromosome, which can contribute to phenotypic diversity and sex-specific traits 1.
Key Points
- X chromosome inactivation occurs in female mammals to achieve dosage compensation for X-linked genes between males (XY) and females (XX) 1.
- The process begins at the X-inactivation center (XIC), which contains the XIST gene that produces a non-coding RNA, recruiting proteins that establish repressive chromatin modifications like DNA methylation and histone deacetylation 1.
- The number of Barr bodies corresponds to the number of X chromosomes minus one, so typical females (XX) have one Barr body, while individuals with conditions like Triple X syndrome (XXX) have two Barr bodies 1.
- Some genes escape inactivation, particularly those in pseudoautosomal regions, contributing to sex-specific traits and certain disease manifestations 1.
Mechanism and Significance
The mechanism of X chromosome inactivation is complex and involves the silencing of one of the two X chromosomes in female cells, resulting in the formation of a Barr body. This process is essential for preventing developmental abnormalities and is influenced by various factors, including the X-inactivation center (XIC) and the XIST gene 1. The significance of X chromosome inactivation lies in its role in ensuring dosage compensation between males and females, which is critical for preventing developmental abnormalities and contributing to sex-specific traits and certain disease manifestations 1.
Variation in the Number of Barr Bodies
The number of Barr bodies can vary depending on the number of X chromosomes present in an individual. Typical females (XX) have one Barr body, while individuals with conditions like Triple X syndrome (XXX) have two Barr bodies 1. Males (XY) normally have no Barr bodies. The variation in the number of Barr bodies can contribute to phenotypic diversity and sex-specific traits, and can also be used as a diagnostic tool for certain genetic disorders 1.
From the Research
X Chromosome Inactivation Mechanism
- The process of X-chromosome inactivation ensures equivalent levels of X-linked gene expression between males and females through the silencing of one of the two X chromosomes in female cells 2.
- The Xist transcript triggers gene silencing in cis by coating the future inactive X chromosome and induces a cascade of chromatin changes, including posttranslational histone modifications and DNA methylation 2.
- Epigenetic marks, such as histone modifications, histone variants, DNA methylation, and ncRNAs, are all enriched on one chromosome, the inactive X chromosome (Xi), to establish its chromosome-wide gene silencing 3.
Significance of X Chromosome Inactivation
- X-chromosome inactivation is an epigenetic process whereby one X chromosome is silenced in mammalian female cells to balance X-linked gene dosage between males and females 4.
- The process is involved in the pathogenesis of several diseases, including X unbalanced rearrangements, X-autosomal balanced translocations, Turner and Klinefelter syndromes, and X-linked diseases 5.
- Incomplete X-chromosome inactivation affects at least 23% of X-chromosomal genes and results in sex biases in gene expression, establishing incomplete XCI as a mechanism that is likely to introduce phenotypic diversity 6.
Variation in the Number of Barr Bodies
- The number of Barr bodies, which are inactive X chromosomes, can vary between individuals and tissues due to incomplete X-chromosome inactivation 6.
- Skewed X-chromosome inactivation, where the process is not fully randomized, can have consequences for the phenotype of some pathologies 5.
- The degree of 'escape' from inactivation varies between genes and individuals, and can result in detectable sex differences in gene expression and phenotypic traits 6.