Comparative Genomics Sheds Light on Mechanisms of Genomic Imprinting
- Thanh H. Vu1 and
- Andrew R. Hoffman1
- Medical Service, VA Palo Alto Health Care System and Department of Medicine, Stanford University, Palo Alto, California 94304, USA
This extract was created in the absence of an abstract.
Genomic imprinting is an epigenetic chromosomal modification in the germ line that leads to preferential expression of one of the two parental alleles in a parent-of-origin-specific manner. A number of recent studies suggest that genomic imprinting is mediated by a set of elements in distinct chromosomal regions that have been termed imprinting centers (IC). By definition, the IC coordinate three activities: the establishment of imprint marks, the maintenance of these imprint marks throughout development, and the implementation of the preferential expression from a specific parental allele (for review, see Ben-Porath and Cedar 2000).
At least four major imprinting models that incorporate recent discoveries have been elucidated: First, the sense/antisense competition model for preferential allelic expression, as exemplified by studies examining the regulation of Igf2r and its associated antisense on mouse chromosome 17 (Box ; Fig.1). Second, the enhancer/chromosomal insulation model developed on the basis of the reciprocal imprinting of Igf2/H19 in human and in mouse (Box ; Fig.2A). Third, the bipartite IC model, which describes the regulation of multiple imprinted genes in a 2-Mb Prader-Willi syndrome/Angelman syndrome(PWS–AS) region of human chromosome 15. Finally, the promoter-specific reciprocal-imprinting model as seen at the human and mouse Gnas locus (Box ; Fig. 2B).
Imprinting of Igf2r: Sense and Antisense Competition Model (Fig. 1)
An elegant model of sense/antisense competition has been proposed by Wutz et al. (1997). On the mouse paternal allele, the IC in region 2 is unmethylated, while promoter region 1 is methylated; antisense Air is transcribed. Aircompetes and turns off the Igf2r sense transcript. On the maternal allele, the IC is methylated and Air is turned off. Promoter region 1 is unmethylated, and Igf2r is transcribed. Two cis-regulatory elements in region 2, the de novo methylation signal (DNS) and the allele-discrimination …
