Disruption of a conserved region of Xist exon 1 impairs Xist RNA localisation and X-linked gene silencing during random and imprinted X chromosome inactivation.
In XX female mammals a single X chromosome is inactivated early in embryonic development, a process that is required to equalise X-linked gene dosage relative to XY males. X inactivation is regulated by a cis-acting master switch, the Xist locus, the product of which is a large non-coding RNA that c...
| Hlavní autoři: | , , , , , , |
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| Médium: | Journal article |
| Jazyk: | English |
| Vydáno: |
2011
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| _version_ | 1826268791737155584 |
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| author | Senner, C Nesterova, T Norton, S Dewchand, H Godwin, J Mak, W Brockdorff, N |
| author_facet | Senner, C Nesterova, T Norton, S Dewchand, H Godwin, J Mak, W Brockdorff, N |
| author_sort | Senner, C |
| collection | OXFORD |
| description | In XX female mammals a single X chromosome is inactivated early in embryonic development, a process that is required to equalise X-linked gene dosage relative to XY males. X inactivation is regulated by a cis-acting master switch, the Xist locus, the product of which is a large non-coding RNA that coats the chromosome from which it is transcribed, triggering recruitment of chromatin modifying factors that establish and maintain gene silencing chromosome wide. Chromosome coating and Xist RNA-mediated silencing remain poorly understood, both at the level of RNA sequence determinants and interacting factors. Here, we describe analysis of a novel targeted mutation, Xist(INV), designed to test the function of a conserved region located in exon 1 of Xist RNA during X inactivation in mouse. We show that Xist(INV) is a strong hypomorphic allele that is appropriately regulated but compromised in its ability to silence X-linked loci in cis. Inheritance of Xist(INV) on the paternal X chromosome results in embryonic lethality due to failure of imprinted X inactivation in extra-embryonic lineages. Female embryos inheriting Xist(INV) on the maternal X chromosome undergo extreme secondary non-random X inactivation, eliminating the majority of cells that express the Xist(INV) allele. Analysis of cells that express Xist(INV) RNA demonstrates reduced association of the mutant RNA to the X chromosome, suggesting that conserved sequences in the inverted region are important for Xist RNA localisation. |
| first_indexed | 2024-03-06T21:15:02Z |
| format | Journal article |
| id | oxford-uuid:3f7e12db-d0ac-494b-962a-7cf8f358fb85 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:15:02Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:3f7e12db-d0ac-494b-962a-7cf8f358fb852022-03-26T14:32:21ZDisruption of a conserved region of Xist exon 1 impairs Xist RNA localisation and X-linked gene silencing during random and imprinted X chromosome inactivation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3f7e12db-d0ac-494b-962a-7cf8f358fb85EnglishSymplectic Elements at Oxford2011Senner, CNesterova, TNorton, SDewchand, HGodwin, JMak, WBrockdorff, NIn XX female mammals a single X chromosome is inactivated early in embryonic development, a process that is required to equalise X-linked gene dosage relative to XY males. X inactivation is regulated by a cis-acting master switch, the Xist locus, the product of which is a large non-coding RNA that coats the chromosome from which it is transcribed, triggering recruitment of chromatin modifying factors that establish and maintain gene silencing chromosome wide. Chromosome coating and Xist RNA-mediated silencing remain poorly understood, both at the level of RNA sequence determinants and interacting factors. Here, we describe analysis of a novel targeted mutation, Xist(INV), designed to test the function of a conserved region located in exon 1 of Xist RNA during X inactivation in mouse. We show that Xist(INV) is a strong hypomorphic allele that is appropriately regulated but compromised in its ability to silence X-linked loci in cis. Inheritance of Xist(INV) on the paternal X chromosome results in embryonic lethality due to failure of imprinted X inactivation in extra-embryonic lineages. Female embryos inheriting Xist(INV) on the maternal X chromosome undergo extreme secondary non-random X inactivation, eliminating the majority of cells that express the Xist(INV) allele. Analysis of cells that express Xist(INV) RNA demonstrates reduced association of the mutant RNA to the X chromosome, suggesting that conserved sequences in the inverted region are important for Xist RNA localisation. |
| spellingShingle | Senner, C Nesterova, T Norton, S Dewchand, H Godwin, J Mak, W Brockdorff, N Disruption of a conserved region of Xist exon 1 impairs Xist RNA localisation and X-linked gene silencing during random and imprinted X chromosome inactivation. |
| title | Disruption of a conserved region of Xist exon 1 impairs Xist RNA localisation and X-linked gene silencing during random and imprinted X chromosome inactivation. |
| title_full | Disruption of a conserved region of Xist exon 1 impairs Xist RNA localisation and X-linked gene silencing during random and imprinted X chromosome inactivation. |
| title_fullStr | Disruption of a conserved region of Xist exon 1 impairs Xist RNA localisation and X-linked gene silencing during random and imprinted X chromosome inactivation. |
| title_full_unstemmed | Disruption of a conserved region of Xist exon 1 impairs Xist RNA localisation and X-linked gene silencing during random and imprinted X chromosome inactivation. |
| title_short | Disruption of a conserved region of Xist exon 1 impairs Xist RNA localisation and X-linked gene silencing during random and imprinted X chromosome inactivation. |
| title_sort | disruption of a conserved region of xist exon 1 impairs xist rna localisation and x linked gene silencing during random and imprinted x chromosome inactivation |
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