Barr Body - Mechanism

Mechanism

A normal human female has only one Barr body per somatic cell, while a normal human male has none.

Mammalian X-chromosome inactivation is initiated from the X inactivation centre or Xic, usually found near the centromere. The center contains twelve genes, seven of which code for proteins, five for untranslated RNAs, of which only two are known to play an active role in the X inactivation process, Xist and Tsix. The centre also appears to be important in chromosome counting: ensuring that random inactivation only takes place when two or more X-chromosomes are present. The provision of an extra artificial Xic in early embryogenesis can induce inactivation of the single X found in male cells.

The roles of Xist and Tsix appear to be antagonistic. The loss of Tsix expression on the future inactive X chromosome results in an increase in levels of Xist around the Xic. Meanwhile, on the future active X Tsix levels are maintained; thus the levels of Xist remain low. This shift allows Xist to begin coating the future inactive chromosome, spreading out from the Xic. In non-random inactivation this choice appears to be fixed and current evidence suggests that the maternally inherited gene may be imprinted.

It is thought that this constitutes the mechanism of choice, and allows downstream processes to establish the compact state of the Barr body. These changes include histone modifications, such as histone H3 methylation and histone H2A ubiquitination, as well as direct modification of the DNA itself, via the methylation of CpG sites. These changes help inactivate gene expression on the inactive X-chromosome and to bring about its compaction to form the Barr body.