Appropriate expression of the mouse H19 gene utilises three or more distinct enhancer regions spread over more than 130 kb

H19 and Igf2 are closely linked, reciprocally imprinted genes which lie on distal chromosome 7 in the mouse. Data suggests that common elements are us ed for expression and imprinting of both genes, and simple models have been proposed based on the presence of a single set of enhancers located downst ream of H19. In this study we have investigated the H19 expression pattern from a 130 kb YAC transgene, which imprints H19 appropriately at ectopic lo ci. However, we show that while enhancers for expression in many cell types are present on the YAC, those for expression in mesodermal components of t he heart, kidney, lung and thymus are located at a greater distance. Based on the available evidence, we conclude that regulation of H19 is complex, r equiring contribution from at least three different sets of cell-type speci fic enhancers. Thus, the mechanism of reciprocal imprinting of H19 and Igf2 utilises different regulatory elements in different cell types during mous e development. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.