Stochastic gene expression and chromosome interactions in protecting the human active X from silencing by XIST
Mammals use X chromosome inactivation to compensate for the sex difference in numbers of X chromosomes. A relatively unexplored question is how the active X is protected from inactivation by its own XIST gene, the long non-coding RNA, which initiates silence of the inactive X. Previous studies of a...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Nucleus |
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| Online Access: | http://dx.doi.org/10.1080/19491034.2020.1850981 |
| Summary: | Mammals use X chromosome inactivation to compensate for the sex difference in numbers of X chromosomes. A relatively unexplored question is how the active X is protected from inactivation by its own XIST gene, the long non-coding RNA, which initiates silence of the inactive X. Previous studies of autosomal duplications show that human chromosome 19 plays a critical role in protecting the active X. I proposed that it genetically interacts with the X chromosome to repress XIST function on the future active X. Here, I show that the type of chromosome 19 duplication influences the outcome of the interaction: the presence of three chromosome 19s is tolerated whereas duplications affecting only one chromosome 19 are not. The different outcomes have mechanistic implications for how chromosome 19 interacts with the future active X, pointing to a role for stochastic gene expression and possibly physical interaction. |
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| ISSN: | 1949-1034 1949-1042 |