Promoter-specific IGF2 imprinting status and its plasticity during human liver development

Area of Science:

• Genetics
• Developmental Biology
• Epigenetics

Background:

• Insulin-like Growth Factor 2 (IGF2) typically shows preferential expression from the paternal allele.
• Maternal IGF2 allele activity is observed during human prenatal and postnatal development, and in tumors.
• The regulation of IGF2 expression involves multiple promoters (P1, P2, P3, P4).

Purpose of the Study:

• To investigate if biallelic expression patterns of IGF2 during postnatal human liver development correlate with coordinated changes in its four promoter activities.
• To determine the promoter-specific activity and imprinting status of IGF2 during human liver development.
• To assess the relationship between IGF2 and H19 gene expression during postnatal liver development.

Main Methods:

• Analysis of IGF2 promoter activity (P1, P2, P3, P4) in human liver specimens from embryonic to adult stages.
• Assessment of H19 gene expression in the same liver samples.
• Evaluation of monoallelic versus biallelic expression patterns for IGF2 and H19.

Main Results:

• Promoters P2, P3, and P4 of IGF2 exhibit monoallelic activity in embryonic, neonatal, and young infant liver.
• In older infants and adults, P2, P3, and P4 promoters can show monoallelic or biallelic activity, sometimes on different parental alleles.
• The H19 gene consistently displays monoallelic expression across all analyzed postnatal liver samples, irrespective of IGF2 patterns.

Conclusions:

• The functional imprinting of IGF2 during postnatal human liver development is specific to individual promoters and enhancers.
• IGF2 imprinting status appears to be largely independent of the closely linked H19 gene.
• Developmental changes in IGF2 expression involve complex, promoter-dependent regulatory mechanisms.