International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 62 - DEVELOPMENTAL PROFILE OF DNA METHYLATION AND GENE EXPRESSION AT THE H19 LOCUS IN MICE LACKING SEQUENCE REQUIRED FOR GENOMIC IMPRINTING

Thorvaldsen J
University of Pennsylvania

Co-Authors: 2) Fedoriw A, 3) Yang G, 4) Nguyen S, 5) Magnuson M, 6) Bartolomei M
Institutions: 2) University of Pennsylvania, 3) University of Pennsylvania, 4) Vanderbilt University, 5) HHMI and University of Pennsylvania

The 2 kb differentially methylated domain (DMD) 5' of H19 is exclusively methylated on the paternal allele throughout development and is required for H19 and Igf2 imprinting. In mice harboring a 1.6 kb deletion of the DMD (ΔDMD) or a 3.8 kb deletion spanning the DMD (Δ3.8kb-5' H19), loss of H19 and Igf2 imprinting is detected in all neonatal tissues (G&D 12:3693, MCB 22:2450). In addition, the DMD is required for full expression of H19 and Igf2. Nevertheless, DMD sequence that remains in the ΔDMD mice, acquires slightly more methylation on the paternal allele than on the maternal allele, indicating that some parental-specific identity is maintained that does not result in differences in parental-specific expression. Here, we investigate allele-specific DNA methylation and gene expression patterns at the H19 locus in the ΔDMD and the Δ3.8kb-5'H19 mice in pre- and post-implantation embryos to determine when loss of H19 and Igf2 imprinting occurs. We detect loss of imprinting at the H19 locus from the deletion alleles after embryo implantation. We have also generated a conditional (floxed) targeted allele of the 1.6 kb DMD sequence. Removal of this sequence in neonatal liver results in loss of Igf2 but not H19 imprinting. Thus, the DMD is required for maintenance of Igf2 but not of H19 imprinting in non-dividing tissues. In summary, analysis of the DMD deletions throughout development is important to determine the sequence requirements and mechanism of imprinting at the H19 locus.


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