Identification of regulatory elements responsible for genomic imprinting in mammals

Genomic imprinting describes the mono-allelic expression of only one of the parental copies of a gene whereas the second allele is silenced by epigenetic modifications, such as DNA methylation or histone modifications. Aims of the here presented project were identification of genetic and epigenetic imprinting control elements and the understanding of their regulatory functions. In two imprinted model regions, the Beckwith-Wiedemann syndrome region (BWS) on chromosome 7, and the Dlk1/Gtl2 region on chromosome 12 in mouse we have identified new imprinted genes and have investigated their allele-specific and tissue-specific expression patterns. Both imprinted regions exhibit a strong evolutionary conservation of gene arrangements in mouse and human.
Though, it is commonly believed that a major function of imprinted genes is the regulation of embryonic growth and development, both regions differ in terms of gene structures and functions: whereas the Gtl2 / Dlk1 region is characterised by numerous snoRNAs and miRNAs that after birth are only expressed in the brain, the BWS region contains several embryonic and placental growth factor and growth repressor genes, and a prominent long non-coding transcript that acts in allele-spefic epigenetic silencing.
Though the genes of both regions appear to be so different, both regions contain central, allele-specific regulatory elements, the so-called imprinting centres. In both regions and in both species, i.e. human and mouse, these elements contain complex patterns of repeated sequence motifs that are the most prominent feature of CpG islands in imprinted regions. Besides these key regulatory elements we identified numerous DNA elements that are highly conserved also in other mammalian species. Reporter gene assays indicate that some tandem repeats or conserved elements might indeed have regulatory potential.
Keywords: Methylation, Imprinting, Beckwith-Wiedemann syndrome
Domain: genetics, epigenomics, comparative genomics, molecular evolution
Involved in the project: Dr. Stephanie Barth
Gilles Gasparoni
Tarang Khare
Sascha Tierling


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Paulsen, M., T. Khare, C. Burgard, S. Tierling and J. Walter. 2005. Evolution of the Beckwith-Wiedemann syndrome region in vertebrates. Genome Research 15: 146-153.



Dr. Martina Paulsen
Universität des Saarlandes
FR 8.2 Genetik
Postfach 151150
66041 Saarbrücken, Germany

Phone: +49 681 302 2795