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Escape from X Inactivation Varies in Mouse Tissues


X inactivation is a female-specific phenomenon that occurs during early development and results in the silencing of one X chromosome in female mammals. However, some genes escape inactivation and remain expressed from both X chromosomes. To date, the identity of escape genes and the molecular mechanisms of this process are still being explored. Here, we use a new binomial model combined with a mouse system with identifiable alleles and skewed X inactivation to identify and further define the chromatin landscape of escape genes in vivo. We find that some escape genes are common to multiple tissues while others are tissue-specific. We also show that expression levels of alleles on the inactive X correlate with factors associated with open chromatin such as RNA Polymerase II and DNase I hypersensitive sites. Additionally, escape genes co-localized with CTCF binding clusters on the Xi, suggesting a role for CTCF binding in delineating regions of escape and inactivation. Our findings represent the first comprehensive analysis of escape in vivo. Identification of tissue-specific escape genes could lead to a better understanding of the underlying causes of sex-linked disorders such as X-linked intellectual disability and Turner syndrome.


Vyšlo v časopise: Escape from X Inactivation Varies in Mouse Tissues. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005079
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005079

Souhrn

X inactivation is a female-specific phenomenon that occurs during early development and results in the silencing of one X chromosome in female mammals. However, some genes escape inactivation and remain expressed from both X chromosomes. To date, the identity of escape genes and the molecular mechanisms of this process are still being explored. Here, we use a new binomial model combined with a mouse system with identifiable alleles and skewed X inactivation to identify and further define the chromatin landscape of escape genes in vivo. We find that some escape genes are common to multiple tissues while others are tissue-specific. We also show that expression levels of alleles on the inactive X correlate with factors associated with open chromatin such as RNA Polymerase II and DNase I hypersensitive sites. Additionally, escape genes co-localized with CTCF binding clusters on the Xi, suggesting a role for CTCF binding in delineating regions of escape and inactivation. Our findings represent the first comprehensive analysis of escape in vivo. Identification of tissue-specific escape genes could lead to a better understanding of the underlying causes of sex-linked disorders such as X-linked intellectual disability and Turner syndrome.


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