597
Views
37
CrossRef citations to date
0
Altmetric
Review

Control of Imprinting at the Gnas Cluster

Pages 207-213 | Received 05 Dec 2007, Accepted 05 Dec 2007, Published online: 02 Jan 2008
 

Abstract

Genomic 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. Misexpression of proteins encoded at the Gnas complex, which is located within the region, can largely account for the imprinting phenotypes. Gnas is a complex locus with extraordinary transcriptional and regulatory complexity. It gives rise to alternatively spliced isoforms that show maternal‑, paternal‑ and biallelic expression as well as a noncoding antisense transcript. The objective of our work at Harwell is to unravel mechanisms controlling the expression of these transcripts. We have performed targeted deletion analysis to test candidate regulatory regions within the Gnas complex and, unlike other imprinted domains, two major control regions have been identified. One controls the imprinted expression of a single transcript and is subsidiary to and must interact with, a principal control region that affects the expression of all transcripts. This principal region contains the promoter for the antisense transcript, expression of which may have a major role in controlling imprinting at the Gnas cluster.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.