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PMID: 10430927 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 16 ·1999-08-03 ·Pages 9242-7

Brenton JD, Drewell RA, Viville S, Hilton KJ, Barton SC, Ainscough JF, Surani MA

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.

MeSH Terms
Alkaline Phosphatase/genetics Animals Chromosome Mapping DNA Methylation Drosophila/genetics Female Gene Library Genes, Reporter Genes, Tumor Suppressor Genetic Techniques Genomic Imprinting Isoenzymes/genetics Male Mice Mice, Inbred Strains Mice, Transgenic Muscle Proteins/genetics RNA, Long Noncoding RNA, Untranslated Testis/enzymology beta-Galactosidase/genetics
Chemicals
H19 long non-coding RNA Isoenzymes Muscle Proteins RNA, Long Noncoding RNA, Untranslated germ-cell AP isoenzyme Alkaline Phosphatase beta-Galactosidase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Brenton J D
Wellcome/Cancer Research Campaign Institute of Cancer and Developmental Biology and Physiological Laboratory, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, United Kingdom.
Drewell R A
Viville S
Hilton K J
Barton S C
Ainscough J F
Surani M A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.16.9242
Published
1999-08-03
Pages
9242-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC17764
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1073/pnas.96.16.9242 PMC Full Text View journal details
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