uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Duration of antisense transcription: A critical component in antisense transcription-mediated bidirectional silencing
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
(English)Manuscript (Other (popular science, discussion, etc.))
URN: urn:nbn:se:uu:diva-92792OAI: oai:DiVA.org:uu-92792DiVA: diva2:166087
Available from: 2005-03-23 Created: 2005-03-23 Last updated: 2010-01-14Bibliographically approved
In thesis
1. Long-range Control of Gene Expression by Imprinting Control Regions During Development and Neoplasia
Open this publication in new window or tab >>Long-range Control of Gene Expression by Imprinting Control Regions During Development and Neoplasia
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Genomic imprinting is an epigenetic phenomenon by which a subset of genes is expressed in a parent of origin specific manner. Most of the imprinted genes are located in clusters. Genetic evidences suggest that genes in imprinted clusters are regulated by Imprinting Control Regions (ICRs). To elucidate the mechanisms by which the imprinting is maintained in clusters, we have chosen a well characterized cluster at the distal end of mouse chromosome 7. This cluster contains 15 imprinted genes and they have been shown to be regulated by H19 and Kcnq1 ICRs.

The mouse H19 ICR, which is shown to have a chromatin insulator function, is implicated in the regulation of H19 and Igf2 genes by interacting with the CTCF protein. It has been documented that CTCF is also involved in the maintenance of differential methylation at the ICR. In this investigation we demonstrated that CTCF maintained differential methylation is lost when we subjected the ICR containing episomal plasmids to de novo methylation machinery of the human choriocarcinoma cell line, JEG3, suggesting that the H19 ICR looses its methylation privilege property under neoplastic conditions.

The Kcnq1 ICR has been implicated in the regulation of 11 imprinted genes. The Kcnq1 ICR is methylated on the active maternal allele but unmethylated on the inactive paternal allele and overlaps an oppositely oriented and paternally expressed gene known as Kcnq1ot1. In this investigation, we documented that the Kcnq1 ICR controls the imprinting of neighboring genes by behaving as a bidirectional silencer and that this function is regulated by antisense RNA Kcnq1ot1. Furthermore, we have documented that duration of antisense transcription plays a critical role in the antisense RNA- mediated silencing.

In conclusion, this thesis provides more insights into the complex mechanistic aspects by which ICRs, control imprinting of genes in clusters during development and neoplasia.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 53 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 29
Molecular biology, Genomic imprinting, Imprinting control region, Antisense RNA, de novo methylation, Molekylärbiologi
National Category
Biochemistry and Molecular Biology
urn:nbn:se:uu:diva-5725 (URN)91-554-6194-8 (ISBN)
Public defence
2005-04-25, Lindahlsalen, Evolutionary Biology Centre, Norbyvägen 18A, Uppsala, 10:00 (English)
Available from: 2005-03-23 Created: 2005-03-23 Last updated: 2009-04-05Bibliographically approved

Open Access in DiVA

No full text

By organisation
Animal Development and Genetics

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 253 hits
ReferencesLink to record
Permanent link

Direct link