NORMAL DEVELOPMENT AND NEOPLASIA - THE IMPRINTING CONNECTION

The observation that a number of autosomal genes are expressed in a pa rent of origin-dependent monoallelic manner has fuelled a frantic rese arch effort into the underlying mechanisms and biological functions of this phenomenon, termed genomic or parental imprinting. The level of intrigue associated with this subject has been heightened by the disco very that the ''transcriptional phenotype'' of some imprinted genes sh ows developmental and tissue-specific variation, and that some imprint ed genes are expressed biallelically in tumors. Here we describe some further examples of variation in the allele-specific transcription of an imprinted gene, human IGF2. Analysis of different sub-clones of an established tumor cell line (Jeg-3) revealed examples of both a switch from monoallelic to biallelic expression, as well as monoallelic expr ession from the opposite parental allele. Examination of IGF2 expressi on in adult human liver clearly demonstrated that the functional impri nting is manifested in a promoter-specific manner. The P1 promoter pro duced biallelically derived transcripts, whereas the remaining three p romoters were utilized in a complex pattern of mono- and biallelic exp ression which varied from sample to sample, These observations emphasi ze the need to re-examine the imprinting phenomenon and its plasticity in terms of the cis elements and trans-acting factors involved in the transcriptional regulation of these genes both in the normal and path ological contexts.