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CTCF recruits Lsh to CTCF target sites genomewide during male germline development: implications for a link between epigenetic reprogramming and BORIS, a CTCF paralogue
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
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(English)Manuscript (Other (popular science, discussion, etc.))
URN: urn:nbn:se:uu:diva-92001OAI: oai:DiVA.org:uu-92001DiVA: diva2:164935
Available from: 2004-09-01 Created: 2004-09-01 Last updated: 2010-01-14Bibliographically approved
In thesis
1. Genomic Imprinting in Development and Evolution
Open this publication in new window or tab >>Genomic Imprinting in Development and Evolution
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Genetic information is encoded by the linear sequence of the DNA double helix, while epigenetic information is overlayed as the packaging of DNA and associated proteins into the chromatin structure. Variations in chromatin structure play a vital role in establishing and maintaining patterns of gene expression during differentiation and development of higher eukaryotes, and disruption of this epigenetic gene regulation can lead to cancer. Mammals display an epigenetic phenomenon known as genomic imprinting, which provides an ideal model system for the study of epigenetics. Genes subject to genomic imprinting are differentially expressed within a single cell depending on the parental origin of the chromosome. Imprinting of the maternally expressed H19 gene and the adjacent paternally expressed Igf2 gene is regulated by the chromatin insulator protein CTCF. The studies presented in this thesis aim to investigate the functional mechanisms of CTCF-dependent gene regulation at the H19/Igf2 locus and at numerous other target sites throughout the genome. We have investigated the role of CTCF and a related protein BORIS in establishing the maternal to paternal imprint transition in chromatin structure at the H19/Igf2 locus in the male germline. We have developed novel microarray based methods to identify and characterize numerous new CTCF target sites throughout the mouse genome. We have shown that CTCF acts as part of the RNA polymerase II complex. We have identified the post-translational modification by addition of ADP-ribose polymers to CTCF, and demonstrated that this modification regulates its insulating ability. The results of these studies of CTCF-dependent epigenetic gene regulation are discussed in light of the evolution of genomic imprinting and chromatin insulators, and a novel role for poly ADP-ribosylation of CTCF in the progression of cancer is proposed.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 74 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 1000
Developmental biology, Utvecklingsbiologi
National Category
Developmental Biology
urn:nbn:se:uu:diva-4491 (URN)91-554-6015-1 (ISBN)
Public defence
2004-09-22, Lindahlsalen, Evolutionary Biology Centre, Norbyvägen 18A, Uppsala, 10:00 (English)
Available from: 2004-09-01 Created: 2004-09-01 Last updated: 2013-05-16Bibliographically approved

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