The mouse H19 locus mediates a transition between imprinted and non-imprinted DNA replication patterns

John M. Greally, Diana J. Starr, Steven Hwang, Liqun Song, Maarit Jaarola, Sharon Zemel

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Genes subject to genomic imprinting generally occur in clusters of hundreds of kilobases. These domains exhibit several gamete of origin-dependent manifestations, including a pattern of asynchronous replication when studied by fluorescence in situ hybridization (FISH). We find a transition from asynchronous replication at the imprinted mouse H19 gene to synchronous replication at the downstream Rpl23 gene, the human homologue of which appears to be non-imprinted. Two-colour FISH demonstrates that this transition is due solely to a difference in replication timing between the upstream and downstream chromatin on the later-replicating (maternal) chromosome. This difference is lost in mice deleted for the H19 gene body and 9.9 kb of upstream DNA when this deletion is maternally inherited, with synchronous replication patterns extending over 110 kb upstream from the deleted area. No effect is seen when the deletion is paternally inherited. The presence of a boundary element in this region has been suggested by observations of position-independent expression of H19-containing transgenes and the blocking of accessibility of downstream enhancers to the upstream Igf2 and Ins2 genes on the maternal chromosome. The FISH studies presented here demonstrate the insulation of replication patterns within the imprinted domain from downstream, non-imprinted chromatin, mediated by an element at the H19 locus which is subject to genomic imprinting.

Original languageEnglish (US)
Pages (from-to)91-95
Number of pages5
JournalHuman Molecular Genetics
Volume7
Issue number1
DOIs
StatePublished - Jan 1998
Externally publishedYes

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DNA Replication
Fluorescence In Situ Hybridization
Genomic Imprinting
Genes
Chromatin
Chromosomes
Insulator Elements
Mothers
Transgenes
Germ Cells
Color
DNA

ASJC Scopus subject areas

  • Genetics

Cite this

The mouse H19 locus mediates a transition between imprinted and non-imprinted DNA replication patterns. / Greally, John M.; Starr, Diana J.; Hwang, Steven; Song, Liqun; Jaarola, Maarit; Zemel, Sharon.

In: Human Molecular Genetics, Vol. 7, No. 1, 01.1998, p. 91-95.

Research output: Contribution to journalArticle

Greally, John M. ; Starr, Diana J. ; Hwang, Steven ; Song, Liqun ; Jaarola, Maarit ; Zemel, Sharon. / The mouse H19 locus mediates a transition between imprinted and non-imprinted DNA replication patterns. In: Human Molecular Genetics. 1998 ; Vol. 7, No. 1. pp. 91-95.
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