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Related Experiment Videos

Genomic imprinting in mice: its function and mechanism

P A Leighton1, J R Saam, R S Ingram

  • 1Department of Molecular Biology, Princeton University, New Jersey 08544, USA.

Biology of Reproduction
|February 1, 1996
PubMed
Summary

Genomic imprinting regulates gene expression based on parental origin. The H19 gene controls imprinting of Igf-2 and Ins-2, impacting intrauterine growth in mammals.

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Area of Science:

  • Epigenetics
  • Developmental Biology
  • Genetics

Background:

  • Genomic imprinting is an epigenetic process causing differential gene expression from parental alleles.
  • Its role in mammalian intrauterine growth regulation is hypothesized but not fully understood.
  • A specific imprinted gene cluster on mouse chromosome 7 involves maternally expressed Mash-2 and H19, and paternally expressed Ins-2 and Igf-2.

Purpose of the Study:

  • To investigate the mechanism and function of genomic imprinting in mammals.
  • To determine the role of the H19 gene in regulating the imprinting of Igf-2 and Ins-2.
  • To explore the relationship between genomic imprinting and intrauterine growth.

Main Methods:

  • Generation of targeted gene disruptions in a specific imprinted region on mouse chromosome 7.
  • Analysis of gene expression patterns for Mash-2, H19, Ins-2, and Igf-2 in wild-type and disrupted mice.
  • Investigation of the molecular mechanisms, including enhancer competition and DNA methylation, involved in imprinting.

Main Results:

  • Targeted disruptions provided evidence supporting the hypothesis that H19 establishes imprinting for Igf-2 and Ins-2.
  • Maternal H19 transcription prevents Igf-2 and Ins-2 expression via enhancer competition.
  • Paternal H19 silencing through DNA methylation allows Igf-2 and Ins-2 expression.

Conclusions:

  • The H19 gene plays a crucial role in regulating the imprinting of Igf-2 and Ins-2.
  • Genomic imprinting, particularly involving H19, likely contributes to the regulation of mammalian intrauterine growth.
  • Understanding these imprinting mechanisms provides insights into developmental processes and potential growth disorders.

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