An enhancer deletion affects both H19 and Igf2 expression. Author P Leighton, J Saam, R Ingram, C Stewart, S Tilghman Publication Year 1995 Type Journal Article Abstract The distal end of mouse Chromosome 7 contains four tightly linked genes whose expression is dependent on their parental inheritance. Mash-2 and H19 are expressed exclusively from the maternal chromosome, whereas Insulin-2 (Ins-2) and Insulin-like growth factor 2 (Igf2) are paternally expressed. The identical expression during development of the 3'-most genes in the cluster, Igf2 and H19, led to the proposal that their imprinting was mechanistically linked through a common set of transcriptional regulatory elements. To test this hypothesis, a targeted deletion of two endoderm-specific enhancers that lie 3' of H19 was generated by homologous recombination in embryonic stem cells. Inheritance of the enhancer deletion through the maternal lineage led to a loss of H19 gene expression in cells of endodermal origin, including cells in the liver, gut, kidney, and lung. Paternal inheritance led to a very similar loss in the expression of Igf2 RNA in the same tissues. These results establish that H19 and Igf2 utilize the same endoderm enhancers, but on different parental chromosomes. Mice inheriting the enhancer deletion from fathers were 80% of normal size, reflecting a partial loss-of-function of Igf2. The reduction was uniformly observed in a number of internal organs, indicating that insulin-like growth factor II (IGFII), the product of Igf2, acts systemically in mice to affect prenatal growth. A modest decline in Ins-2 RNA was observed in the yolk sac. In contrast Mash-2, which is expressed in spongiotrophoblast cells of the placenta, was unaffected by the enhancer deletion. Keywords Animals, Gene Expression Regulation, Developmental, Female, Male, Base Sequence, In Situ Hybridization, Mice, Molecular Sequence Data, Enhancer Elements, Genetic, Transcription Factors, DNA-Binding Proteins, RNA, Basic Helix-Loop-Helix Transcription Factors, Endoderm, Insulin, Genomic Imprinting, Muscle Proteins, RNA, Long Noncoding, RNA, Untranslated, Stem Cells, Embryonic and Fetal Development, Crosses, Genetic, Heterozygote, Gene Targeting, Insulin-Like Growth Factor II, Sequence Deletion Journal Genes Dev Volume 9 Issue 17 Pages 2079-89 Date Published 09/1995 Alternate Journal Genes Dev. Google ScholarBibTeXEndNote X3 XML