Mammalian females have 2 X chromosomes, while males have 1 X chromosome and the sex-determining Y chromosome. Long ago, these were a pair of chromosomes, and contained around 1000 genes, but as the Y chromosome became specialized for its role in sex-determination, it lost many of these genes. This poses a ‘dosage’ problem as females now had twice the copy number as males – so the process of X-chromosome inactivation came to the rescue and silences most genes on one X in females. We study how this inactivation occurs, and then is maintained in all cells of a female – as is seen in a calico cat. The link will take you to ‘why all the cats’.
X-chromosome inactivation is initiated by the XIST RNA – one of the first long non-coding RNAs to be discovered. XIST ‘coats’ the inactive X chromosome, recruiting proteins to the chromosome from which it is transcribed. We are exploring how XIST interacts with DNA and proteins to silence an X. See details here about XIST and the mechanism of X-chromosome inactivation.
Surprisingly, not all the genes on the inactive X chromosome are silenced, and we are studying these exceptions to better understand the silencing process, and because these genes are expressed differently between males and females. See this link for details on the Escapees on the inactive X chromosome.
Funding for our research is provided by:
|The Canadian Institutes of Health Research|
|The Natural Sciences and Engineering Research Council|