Structural and functional comparison of the human and murine IGF2R genes: A search for imprinting signals

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133845

Kalscheuer, V; Riesewijk, A; Schepens, M ^[1]

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1. University Hospital Nijmegen (Netherlands); and others

We have demonstrated that the human insulin-like growth factor II receptor gene is equally expressed on paternally and maternally derived chromosomes. This is unexpected since in mice, the Igf2r gene is subject to imprinting and is expressed exclusively from the maternally inherited chromosome. Structural comparison between the human and the murine IGF2R gene provides a unique opportunity to identify sequence motifs that play a role in the initiation and maintenance of imprinting. Recently, two CpG-rich regions in the murine Igf2r gene have been identified that are differentially methylated on maternally and paternally derived chromosomes, one surrounding the site for initiation of transcription and the other in the second intron. In order to search for corresponding CpG islands in the human IFG2R gene and as a prerequisite for the determination of its structure, we have isolated a YAC clone containing the entire human gene as well as 8 kb of 5{prime} flanking sequences. The insert has been subcloned as a cosmid contig. Two CpG islands have been identified, one in the promoter region and the other in intron 2. Therefore, with respect to imprinting both structural motifs seem to be conserved. Sequence comparison of the first CpG island including the promoter region of human and murine IGF2R genes revealed 70% homology. Sequence analysis of the second CpG island is in progress. Preliminary results of the methylation studies suggest that at least one partially methylated site is embedded in the second CpG island. We are presently investigating if methylation is restricted to one parental gene copy. Finally, the functional significance of these motifs for differential imprinting is being ascertained by YAC transfer into murine embryonic stem cells and the generation of transgenic animals carrying the human IGF2R gene.

• OSTI ID: 133845
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CHROMOSOMES
COMPARATIVE EVALUATIONS
CONTIGS
DNA
DNA SEQUENCING
DNA-CLONING
GENE REPRESSORS
GENES
GENETICS
GROWTH FACTORS
HUMAN POPULATIONS
METHYLATION
MICE
NUCLEOTIDES
RECEPTORS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRANSCRIPTION
YEASTS