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Role of histone methylation in paternal transmission of epigenetic information

Brykczynska, Urszula. Role of histone methylation in paternal transmission of epigenetic information. 2010, PhD Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_9275

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Abstract

During the development of multi-cellular organisms, one genome gives rise to multiple differentiated cell types. This is achieved by sequence specific transcription factors and different epigenetic mechanisms, which collaborate in reading the genetic information. These epigenetic mechanisms coordinate the establishment and maintenance of transcriptional programs in a lineage specific manner during development. However, very little is known whether such epigenetic information can be also passed to the next generation.
Mammalian gametes may differ in their potential to transmit chromatin encoded epigenetic information. The oocyte genome is organized in a nucleosomal configuration with DNA wrapped around histones that carry various post translational modifications. By contrast, the paternal genome undergoes a major reorganization during the last stages of spermatogenesis. Most of histones are replaced by protamines, which after fertilization, are exchanged by maternally provided histones. Nevertheless, approximately 10% of histones are retained in human spermatozoa, raising a possibility for a paternal, epigenetic contribution to the next generation.
In this thesis, I aimed to determine the genomic localisation of histones retained in sperm and to analyze their potential to influence transcription after fertilization. We show that histones isolated from mouse and human spermatozoa are carrying multiple post translational modifications, many of which have functions in gene regulation. In our genome wide analysis of human promoters, we demonstrate that two of these marks, Trithorax/Set1 mediated dimethylation of lysine 4 of histone H3 (H3K4me2) and Polycomb mediated trimethylation of lysine 27 of histone H3 (H3K27me3), occupy functionally defined groups of genes. H3K4me2-marked promoters control genes with functions in spermatogenesis and cellular homeostasis, suggesting that this mark reflects germline transcription. By contrast, multiple developmental regulators, which are Polycomb targets in pluripotent somatic cells, are marked by H3K27me3 in human sperm. Similarly to somatic cells, the presence of this mark correlates with gene repression during spermatogenesis and in the early embryo. We propose a model in which H3K27me3, transmitted by sperm, assures repression of developmental regulators at the totipotent stage of the preimplantation development. Finally, we demonstrate that a number of these developmental regulators are also marked by H3K27me3 in mouse spermatozoa, implicating an evolutionary conserved role for histone methylation in the paternal transmission of epigenetic information.
Advisors:Peters, Antoine
Committee Members:Hofsteenge, Jan and Gasser, Susan
Faculties and Departments:09 Associated Institutions > Friedrich Miescher Institut FMI
Item Type:Thesis
Thesis no:9275
Bibsysno:Link to catalogue
Number of Pages:121 Bl.
Language:English
Identification Number:
Last Modified:30 Jun 2016 10:41
Deposited On:07 Jan 2011 10:09

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