Identify the key mechanism that determines which X remains a

Identify the key mechanism that determines which X remains active and which X becomes inactive.

Solution

In normal human females, only one X chromosome is transcriptionally active, the other X chromosome remains condensed as heterochromatin and is called as sex chromatin or Barr body. Formation of Barr body ensures that cells of both males and females have same number of active X chromosomes and thus synthesise equal amount of products encoded by X linked genes.

This inactivation of one of the two X chromosome in each cell is called Lyonization, after the name of British researcher Mary Lyon. She proposed that;

Inactivation of X chromosome in females occurs during early stages of embryonic development and this Inactivation of X chromosome in embryo is a random process, so that paternally derived and maternally derived X chromosomes stands equal chance of becoming inactivated in any given cell.

MECHANISM OF INACTIVATION :

The mechanism of Inactivation is initiated by a non coding RNA molecule called XIST RNA.

There is a region on X chromosome called as X-Inactivation center (XIC) located on proximal end of X chromosome. Genetic expression of this region occurs only on chromosome that is inactivated. This region carries about 4 genes one of which is X-Inactivation specific transcript (XIST). The RNA transcribed by this gene is called XIST RNA. This RNA is large (about 17kb long) and is not translated. It does not diffuse into nucleoplasm,but accumulates along the length of chromosome just before it is Inactivated.

Thus RNA product of XIST gene spread over and coat the X chromosome bearing the gene that produced it ,creating some sort of molecular \"cage\" that entraps it leading to its Inactivation.

Thus X chromosome in which XIST gene is transcribed to form XIST RNA becomes inactive (due to coating of this X chromsome by XIST RNA) while as the other X chromosome remains active.