X Chromosome Inactivation

X-chromosome inactivation is the process in which one of the two X-chromosomes in a female mammal becomes inactivated. This process takes place due to dosage compensation - the mechanism which maintains similar amounts of X-linked gene products between males and females. This is required because with females having 2 X chromosomes (XX), they have the potential for producing twice the amount of X-linked gene products.

X-chromosome inactivation happens through forming Barr bodies - these are inactive X chromosomes, seen as condensed and darkly staining bodies in the nuclei of cells in females.

As females have 2 X chromosomes (one from the father and one from the mother), how do we know which one is inactivated? The Lyon Hypothesis is a theory for this (widely accepted now for placental mammals), which states that inactivation takes place at random at an early stage during development. It also hypothesises that once that X-chromosome has been inactivated, the same X-chromosome will be inactivated in all of the offspring cells.

X-chromosome inactivation is carried out in 2 main steps:

1. The cell checks the number of X-chromosomes present in the cell
2. The cell selects 1 X-chromosome to be active, while the rest are inactivated

The mechanism begins at a site called the XIC - X inactivation centre. This produces two main non-coding RNA transcripts - Xist gene and Tsix gene. It is known that the Xist gene is active on the X-chromosome which is to be inactivated. This leads to the gene producing an RNA molecule which coats that X-chromosome (spreading outwards from the XIC). Probably by recruiting other protein complexes, this X-chromosome is packaged into a dense and compacted form of chromatin, which is called heterochromatin.