Publications by authors named "Christine M Williamson"
Macro long non-coding RNAs (lncRNAs) play major roles in gene silencing in inprinted gene clusters. Within the imprinted cluster, the paternally expressed lncRNA downregulates its sense counterpart . To explore the mechanism of action of , we generated two new knock-in alleles to truncate upstream and downstream of the promoter.
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- DNA methylation is key for genomic imprinting, where genes are marked differently in male and female gametes; in females, specific transcription is necessary for this process at certain regions called differentially methylated regions (DMRs).
- The study focuses on the Gnas gene cluster, showing that in female mice, a transcript called Nesp facilitates methylation at DMRs, leading to expression of Gnas and repression of Gnasxl; while in male mice, Nesp is usually repressed, keeping Gnas turned off and Gnasxl active.
- Using mutant mice, researchers found that when Nesp is abnormally expressed in males, it triggers methylation of DMRs in som
Article Synopsis
- The Gnas cluster is important for things like body weight, how we use energy, eating habits, and overall health.
- Scientists created two new mouse mutants to study how certain genes affect growth and health after being passed down from parents.
- One mutant leads to slower growth in baby mice but eventually catches up, while the other causes more serious growth problems and suggests that a specific protein (XLαs) helps manage bone and fat health in adults.
There is increasing evidence that non-coding macroRNAs are major elements for silencing imprinted genes, but their mechanism of action is poorly understood. Within the imprinted Gnas cluster on mouse chromosome 2, Nespas is a paternally expressed macroRNA that arises from an imprinting control region and runs antisense to Nesp, a paternally repressed protein coding transcript. Here we report a knock-in mouse allele that behaves as a Nespas hypomorph.
View Article and Find Full Text PDFThe MouseBook (http://www.mousebook.org) databases and web portal provide access to information about mutant mouse lines held as live or cryopreserved stocks at MRC Harwell.
View Article and Find Full Text PDFGenomic imprinting is a form of epigenetic regulation in mammals whereby a small subset of genes is silenced according to parental origin. Early work had indicated regions of the genome that were likely to contain imprinted genes. Distal mouse chromosome 2 is one such region and is associated with devastating but ostensibly opposite phenotypes when exclusively maternally or paternally derived.
View Article and Find Full Text PDFGenomic imprinting is a form of epigenetic regulation in mammals whereby a small subset of genes is silenced according to parental origin. Early work had indicated regions of the genome that were likely to contain imprinted genes. Distal mouse chromosome 2 is one such region and is associated with devastating but ostensibly opposite phenotypes when exclusively maternally or paternally derived.
View Article and Find Full Text PDFGenomic imprinting results in allele-specific silencing according to parental origin. Silencing is brought about by imprinting control regions (ICRs) that are differentially marked in gametogenesis. The group of imprinted transcripts in the mouse Gnas cluster (Nesp, Nespas, Gnasxl, Exon 1A and Gnas) provides a model for analyzing the mechanisms of imprint regulation.
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- Genomic imprinting leads to the silencing of specific gene alleles based on whether they come from the mother or the father, regulated by special regions that can affect nearby genes significantly.
- Researchers have identified two important regions that control imprinting in the Gnas gene cluster on mouse chromosome 2, finding that one region affects the expression of Gnas itself while the other may influence related transcripts.
- A study showed that deleting a specific methylation region linked to paternal expression of Gnas can reverse certain abnormalities in mice with a maternal Gnas mutation, indicating a complex control system for this gene and its neighbors.
The Gnas locus in the mouse is imprinted with a complex arrangement of alternative transcripts defined by promoters with different patterns of monoallelic expression. The Gnas transcript is subject to tissue-specific imprinted expression, Nesp is expressed only from the maternal allele, and Gnasxl is expressed only from the paternal allele. The mechanisms controlling these expression patterns are not known.
View Article and Find Full Text PDFThe Gnas locus on mouse Chr 2 represents a unique cluster of overlapping imprinted genes. Three of these in the order Nesp--Gnasxl--Gnas are transcribed in the sense direction with Nesp having maternal-specific expression, Gnasxl having paternal expression, and Gnas as being biallelically expressed in most tissues. A fourth imprinted gene, Nespas, is paternally expressed, lies antisense to Nesp, and expresses an unspliced transcript.
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