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 have 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 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 would be subject to inactivation, when located on the X chromosome.
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
Cotton AM, Chen CY, Lam LL, Wasserman WW, Kobor MS, Brown CJ. 2014 Spread of X-chromosome inactivation into autosomal sequences: role for DNA elements, chromatin features and chromosomal domains. Hum Mol Genet. 23(5):1211-23. PMID: 24158853
Bradley Balaton ‘mined’ existing data to evaluate the heterochromatin features of the promoters and enhancers of ‘escapees’:
BP Balaton, CJ Brown. 2021.Contribution of genetic and epigenetic changes to escape from X-chromosome inactivation. Epigenetics & Chromatin 14 (1), 1-22. PMID: 34187555
And also found that some genes escape from X-chromosome inactivation in most species, while others are clade-specific; with most escapees in humans and least in mice
BP Balaton, O Fornes, WW Wasserman, CJ Brown. 2021. Cross-species examination of X-chromosome inactivation highlights domains of escape from silencing. Epigenetics & chromatin 14 (1), PMID: 3597016