Genes that Escape from X-chromosome inactivation

In humans approximately 15% of X-linked genes continue to be expressed from the inactive X chromosome, and another ~ 15% of genes are expressed from the inactive X in only some females, populations, or cell types.  These ‘exceptions to the rule’ can inform our understanding of the silencing process.  In addition, they may account for some of the differences that are seen between men and women (sexual dimorphism).  It is generally believed that hormones are the biggest reason for differences between men and women; however the differences in gene expression between the sex chromosomes (women are generally XX while men are XY) are now known to be important contributors as well.

We recently published a comprehensive survey of the genes that escape from X inactivation.

Balaton BP, Cotton AM, Brown CJ. 2015. Derivation of consensus inactivation status for X-linked genes from genome-wide studies. Biol Sex Differ. 2015 Dec 30;6:35. PMID: 26719789

We also recently reviewed this topic:

Balaton, BP, and Brown CJ. 2016. Escape artists of the X chromosome. Trends in Genetics. PMID: 27103486

To understand the DNA elements that control whether a gene is subject to, or escapes from, X inactivation, we are studying what happens when genes that escape from inactivation in humans are put in a region of the mouse X chromosome that is subject to inactivation.

In general we have found that most regions of the human genome are subject to inactivation.

Yang C, McLeod AJ, Cotton AM, de Leeuw CN, Laprise S, Banks KG, Simpson EM, Brown CJ. 2012 Targeting of Over 1.5 Mb of Human DNA into the Mouse X Chromosome Reveals Presence of cis-acting Regulators of Epigenetic Silencing. Genetics. 192: 12981-1293. PMID: 23023002