A silencer element identified in Drosophila is required for imprinting of H19 reporter transgenes in mice

A silencer element identified in Drosophila is required for imprinting of H19 reporter transgenes in mice

Wellcome/Cancer Research Campaign Institute of Cancer and Developmental Biology and Physiological Laboratory, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, United Kingdom

Communicated by Mary F. Lyon, Medical Research Council, Oxon, United Kingdom, and approved June 8, 1999 (received for review April 13, 1999)

Abstract

The H19 gene is subject to genomic imprinting because it is methylated and repressed after paternal inheritance and is unmethylated and expressed after maternal inheritance. We recently identified a 1.1-kb control element in the upstream region of the H19 gene that functions as a cis-acting silencer element in Drosophila. Here we investigate the function of this element in mice. We demonstrate that both H19–lacZ and H19–PLAP reporter transgenes can undergo imprinting with repression and hypermethylation after paternal transmission at many integration sites. However, transgenes that were deleted for the 1.1-kb silencer element showed loss of paternal repression, but they did not show marked changes in the paternal methylation of the remaining upstream region. This study demonstrates that the 1.1-kb control element identified in Drosophila is required to silence paternally transmitted H19 minitransgenes in mice.

Footnotes

↵ * Present address: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur, College de France, 1 rue Laurent Fries BP 163, 67404 Illkirch Cedex, Strasbourg, France.
↵ † To whom reprint requests should be addressed. E-mail: as10021{at}mole.bio.cam.ac.uk.
ABBREVIATIONS:

DMD,

differentially methylated domain;

PLAP,

placental alkaline phosphatase;

YAC,

yeast artificial chromosome