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Related Experiment Videos

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

J M Greally1, D J Starr, S Hwang

  • 1Department of Genetics, Yale University School of Medicine, 333 Cedar Street, PO Box 208081, New Haven, CT 06520-8081, USA.

Human Molecular Genetics
|February 28, 1998
PubMed
Summary

Genomic imprinting involves asynchronous replication in imprinted gene clusters. A boundary element at the H19 gene locus insulates replication timing, demonstrating imprinted control over chromatin replication patterns.

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Area of Science:

  • Epigenetics and Gene Regulation
  • Genomic Imprinting
  • Chromatin Biology

Background:

  • Genomic imprinting involves parent-of-origin-specific gene expression.
  • Imprinted genes often reside in large clusters exhibiting gamete of origin-dependent characteristics, such as asynchronous replication.
  • The H19 gene locus is a well-studied example of genomic imprinting.

Purpose of the Study:

  • To investigate the replication timing patterns within imprinted gene clusters.
  • To identify the role of the H19 locus in regulating replication timing boundaries.
  • To determine if an imprinting-dependent boundary element exists at the H19 locus.

Main Methods:

  • Utilized two-colour fluorescence in situ hybridization (FISH) to analyze replication timing.

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  • Studied replication patterns in wild-type mice and mice with deletions at the H19 locus.
  • Examined both maternally and paternally inherited deletions to assess parent-of-origin effects.

    • Main Results:

    • Observed a transition from asynchronous replication at the imprinted H19 gene to synchronous replication at the downstream Rpl23 gene on the maternal chromosome.
    • Demonstrated that this replication timing difference is due to an imprinting-dependent boundary element at the H19 locus.
    • Showed that deletion of the H19 gene body and upstream DNA abolished the asynchronous replication boundary on the maternal chromosome.

    Conclusions:

    • The H19 locus contains an imprinting-dependent boundary element that insulates replication timing.
    • This boundary element controls the asynchronous replication characteristic of imprinted domains.
    • Genomic imprinting plays a crucial role in establishing and maintaining distinct replication timing patterns within imprinted gene clusters.