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CTCF binding and higher order chromatin structure of the H19 locus are maintained in mitotic chromatin
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2005 (English)In: European Molecular Biology Organization, ISSN 0261 - 4189, Vol. 24, no 18, 10- p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2005. Vol. 24, no 18, 10- p.
URN: urn:nbn:se:uu:diva-95339OAI: oai:DiVA.org:uu-95339DiVA: diva2:169513
Available from: 2007-01-10 Created: 2007-01-10 Last updated: 2009-04-05Bibliographically approved
In thesis
1. Epigenetic Regulation of Genomic Imprinting and Higher Order Chromatin Conformation
Open this publication in new window or tab >>Epigenetic Regulation of Genomic Imprinting and Higher Order Chromatin Conformation
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Epigenetisk reglering av genetisk prägling och kromatinets konformation
Abstract [en]

The genetic information encoded by the DNA sequence, can be expressed in different ways. Genomic imprinting is an epigenetic phenomenon that results in monoallelic expression of imprinted genes in a parent of origin-dependent manner. Imprinted genes are frequently found in clusters and can share common regulatory elements. Most of the imprinted genes are regulated by Imprinting Control Regions (ICRs). H19/Igf2 region is a well known imprinted cluster, which is regulated by insulator function of ICR located upstream of the H19 gene. It has been proposed that the epigenetic control of the insulator function of H19 ICR involves organization of higher order chromatin interactions.

In this study we have investigated the role of post-translational modification in regulating insulator protein CTCF (CCCTC-binding factor). The results indicated novel links between poly(ADP-ribosyl)ation and CTCF, which are essential for regulating insulators function.

We also studied the higher order chromatin conformation of Igf2/H19 region. The results indicated there are different chromatin structures on the parental alleles. We identified CTCF-dependent loop on the maternal allele which is different from the paternal chromatin and is essential for proper imprinting of Igf2 and H19 genes. The interaction of H19 ICR with Differentially Methylated Regions (DMRs) of Igf2 in a parent-specific manner maintains differential epigenetic marks on maternal and paternal alleles.

The results indicate that CTCF occupies specific sites on highly condensed mitotic chromosomes. CTCF-dependent long-range key interaction on the maternal allele is maintained during mitosis, suggesting the possible epigenetic memory of dividing cells.

In this study, we developed a new method called Circular Chromosome Conformation Capture (4C) to screen genome-wide interactions with H19 ICR. The results indicated there are wide intra- and inter-chromosomal interactions which are mostly dependent on CTCF-binding site at H19 ICR.

These observations suggest new aspects of epigenetic regulation of the H19/Igf2 imprinted region and higher order chromatin structure.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 59 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 262
Developmental biology, Epigenetic, Imprinting, Chromatin, CTCF, H19 ICR, 4C, Utvecklingsbiologi
National Category
Biological Sciences
urn:nbn:se:uu:diva-7435 (URN)978-91-554-6772-2 (ISBN)
Public defence
2007-01-31, Lindahlsalen, EBC, Norbyvägen 18A, Uppsala, 10:00 (English)
Available from: 2007-01-10 Created: 2007-01-10 Last updated: 2010-01-08Bibliographically approved

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