Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The Functional Significance and Chromatin Organisation of the Imprinting Control Regions of the H19 and Kcnq1 Genes
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology, Animal Development and Genetics.
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Genomic imprinting is a phenomenon through which a subset of genes are epigenetically marked during gemtogenisis. This mark is maintained in the soma to often manifest parent of origin-specific monoalleleic expresson patterns. Genetics evidence suggests that gene expression patterns in mprinted genes, which are frequently organised in clusters, are regulated by the imprinting control regions (ICR). This thesis is mainly focused on the mechanisms through which the ICRs control the imprinting in the cluster, containing the Kcnq1, Igf2 and H19 genes, located at the distal end of mouse chromosome 7.

The H19 ICR, located in the 5' flank of the H19 gene represses paternal H19 and maternal Igf2 expression, respectively, but has no effect on Kcnq1 expression, which is controlled by another ICR located at the intron 10 of the Kcnq1 gene. This thesis demonstrates that the maternal H19 ICR allele contains several DNase I hypersensitive sites, which map to target sites for the chromatin insulator protein CTCF at the linker regions between the positioned nucleosomes. The thesis demonstrates that the H19 ICR acts as a unidirectional insulator and that this property invovles three nucleosome positioning sites facilitating interaction between the H19 ICR and CTCF. The Kcnq1 ICR function is much more complex, since it horbours both lineage-specific silencing functions and a methylation sensitive unidirectional chromatin insulator function. Importantly, the thesis demonstrates that the Kcnq1 ICR spreads DNA methylation into flanking region only when it is itself unmethylated. Both the methylation spreading and silencing functions map to the same regions.

In conclusion, the thesis has unraveled and unrivalled complexity of the epigenetic control and function of short strtches of sequences. The epigenetic status of these cis elements conspires to control long-range silencing and insulation. The manner these imprinting control regions can cause havoc in expresson domains in human diseases is hence emerging.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2004. , p. 40
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 941
Keyword [en]
Molecular genetics, DNA methylation, Imprinting control region, Chromatin, Insulator, Nucleosome positioning
Keyword [sv]
Genetik
National Category
Genetics
Identifiers
URN: urn:nbn:se:uu:diva-4002ISBN: 91-554-5878-5 (print)OAI: oai:DiVA.org:uu-4002DiVA, id: diva2:164094
Public defence
2004-03-19, Lindahlsalen, EBC, Uppsala, 10:00
Opponent
Supervisors
Available from: 2004-02-20 Created: 2004-02-20 Last updated: 2011-11-10Bibliographically approved
List of papers
1. The 5' flank of mouse H19 in an unusual chromatin conformation unidirectionally blocks enhancer-promoter communication
Open this publication in new window or tab >>The 5' flank of mouse H19 in an unusual chromatin conformation unidirectionally blocks enhancer-promoter communication
Show others...
2000 (English)In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 10, no 8, p. 449-457Article in journal (Refereed) Published
Keyword
Alleles, Animals, Blotting; Southern, Cell Line, Chromatin/*chemistry, Enhancer Elements (Genetics), Female, Fetus, Humans, Insulin-Like Growth Factor II/*genetics, Male, Mice, Muscle Proteins/*genetics/metabolism, Plasmids, Polymerase Chain Reaction, Promoter Regions (Genetics), Protein Conformation, RNA; Untranslated, Terminal Repeat Sequences, Transformation; Genetic
National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-24765 (URN)10.1016/S0960-9822(00)00442-5 (DOI)10801414 (PubMedID)
Available from: 2007-02-08 Created: 2007-02-08 Last updated: 2017-12-07Bibliographically approved
2. Mutiple nucleosome positioning sites regulate the CTCF-mediated insulator function of the H19 impriting control region
Open this publication in new window or tab >>Mutiple nucleosome positioning sites regulate the CTCF-mediated insulator function of the H19 impriting control region
Show others...
2002 In: Molecular and Cellular Biology, Vol. 22, no 10, p. 3339 - 3344Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-91380 (URN)
Available from: 2004-02-20 Created: 2004-02-20Bibliographically approved
3. A differentially methylated imprinting control region within the Kcnq1 Locus harbors a methylation-sensitive chromatin insulator
Open this publication in new window or tab >>A differentially methylated imprinting control region within the Kcnq1 Locus harbors a methylation-sensitive chromatin insulator
Show others...
2002 In: The Journal of biological chemistry, Vol. 277, no 20, p. 18106 - 18110Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-91381 (URN)
Available from: 2004-02-20 Created: 2004-02-20Bibliographically approved
4. Bidirectional silencing and DNA methylation-sensitive methylation-spreading properties of the Kcnq1 imprinting control region map to the same regions
Open this publication in new window or tab >>Bidirectional silencing and DNA methylation-sensitive methylation-spreading properties of the Kcnq1 imprinting control region map to the same regions
Show others...
2003 In: The journal of biological chemistry, Vol. 278, no 11, p. 9514 - 9519Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-91382 (URN)
Available from: 2004-02-20 Created: 2004-02-20Bibliographically approved

Open Access in DiVA

fulltext(439 kB)1336 downloads
File information
File name FULLTEXT01.pdfFile size 439 kBChecksum SHA-1
ef2395e0a47266a822e4061373d0847404f2ffe38a0a21cb5aa56dc9b2d3612c9862ade7
Type fulltextMimetype application/pdf
Buy this publication >>

By organisation
Animal Development and Genetics
Genetics

Search outside of DiVA

GoogleGoogle Scholar
Total: 1336 downloads
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

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 1043 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf