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A cis-acting control region is required exclusively for the tissue-specific imprinting of Gnas

journal contribution
posted on 2023-06-07, 22:55 authored by Christine M Williamson, Simon T Ball, Wade T Nottingham, Judith A Skinner, Antonius Plagge, Martin D Turner, Nicola Powles, Tertius Hough, David Papworth, William D Fraser, Mark Maconochie, Jo Peters
Genomic imprinting brings about allele-specific silencing according to parental origin1. Silencing is controlled by cis-acting regulatory regions that are differentially marked during gametogenesis and can act over hundreds of kilobases to silence many genes2, 3, 4, 5, 6. Two candidate imprinting control regions (ICRs) have been identified at the compact imprinted Gnas cluster on distal mouse chromosome 2, one at exon 1A upstream of Gnas itself7 and one covering the promoters for Gnasxl and the antisense Nespas (ref. 8). This imprinted cluster is complex, containing biallelic, maternally and paternally expressed transcripts that share exons9. Gnas itself is mainly biallelically expressed but is weakly paternally repressed in specific tissues10. Here we show that a paternally derived targeted deletion of the germline differentially methylated region at exon 1A abolishes tissue-specific imprinting of Gnas. This rescues the abnormal phenotype of mice with a maternally derived Gnas mutation11, 12. Imprinting of alternative transcripts, Nesp, Gnasxl and Nespas (ref. 13), in the cluster is unaffected. The results establish that the differentially methylated region at exon 1A contains an imprinting control element that specifically regulates Gnas and comprises a characterized ICR for a gene that is only weakly imprinted in a minority of tissues. There must be a second ICR regulating the alternative transcripts.

History

Publication status

  • Published

Journal

Nature Genetics

ISSN

1061-4036

Publisher

Nature Publishing Group

Volume

36

Page range

894-899

Pages

6.0

Department affiliated with

  • Neuroscience Publications

Notes

On this collaboration, my contribution was to generate the transgenic mice, as well as contributing towards to the experimental design. I also helped preparing the manuscript both pre-review and in meeting the reviewers additional requests. This was reflected with a prominent authorship for myself and my student (NP).

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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