CHROM.ORG.IMP.CLUS · Regulation of gene expression of the imprinted H19-Igf2 cluster by higher order chromosomal organisation

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Project objective

Higher order chromosomal organisation is an important determinant of gene regulation. Cis-regulatory elements, such as enhancers, Locus Control Regions and insulators that are spread over the DNA can be brought into close proximity. Three new applications have recently been developed to study this organisation: Chromatin Conformation Capture (3C), RNA-TRAP and the UAS-Gal4 method. Imprinted genes are expressed solely from either the maternally or paternally inherited alleles and many are clustered in the ge nome. These genes are marked epigenetically by DNA methylation and histon modifications. The imprinted H19-Igf2 cluster has been studied extensively. The paternally expressed gene insulin-like growth-factor 2 (Igf2) is separated by approximately 100 kb fro m the maternally expressed non-coding gene H19 on mouse distal chromosome 7. Recently it was shown that distally located regions in this cluster have paternal-specific interactions. Here, I propose to study the higher order organisation of the imprinted H19 -Igf2 locus, using a combination of the three new techniques.In the first place I am interested in regulatory elements that are in brought in proximity of the H19 DMR, and particularly of interest are differences in secondary structure between the paterna l and maternal inherited alleles. The contribution of single elements can be studies with various mice mutants established in the lab of W. Reik. Secondly I will study interactions of various enhancers downstream of Igf2 and the paternal copy of the gene in various tissues. This study will also reveal the placental specific enhancer sequences. In addition to determining DNA sequences involved in the higher order chromatin organisation of the H19-Igf2 locus, I would like to study proteins that are involved. This study will have an important contribution to our understanding of regulation of gene expression by higher order chromosomal organisation.

Original text from CORDIS.

Participants

• The Babraham Institute · CambridgeCoordinatorUnited Kingdom

Links

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