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Related Experiment Videos

Developmental acquisition of enhancer function requires a unique coactivator activity

S Majumder1, Z Zhao, K Kaneko

  • 1University of Texas MD Anderson Cancer Center, Houston 77030, USA.

The EMBO Journal
|April 1, 1997
PubMed
Summary

Enhancer function in early mouse embryos requires a novel coactivator activity that emerges during development. This activity is essential for gene regulation, appearing only after the one-cell stage.

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Area of Science:

  • Developmental Biology
  • Gene Regulation
  • Epigenetics

Background:

  • Enhancers are regulatory DNA elements that typically stimulate gene promoters.
  • Chromatin-mediated repression is a known mechanism affecting gene expression.
  • The precise timing and requirements for enhancer function during early embryonic development remain incompletely understood.

Purpose of the Study:

  • To investigate the role of enhancers and their associated factors during early mouse embryogenesis.
  • To determine the developmental stage at which enhancers gain the ability to stimulate promoters in vivo.
  • To identify the molecular components necessary for enhancer function in the pre-implantation mouse embryo.

Main Methods:

  • Microinjection of plasmid DNA encoding genes and regulatory elements into mouse oocytes and embryos.

Related Experiment Videos

  • Utilizing expression vectors (e.g., GAL4:VP16) to provide specific transcription factors.
  • Assessing enhancer-promoter interactions and gene expression at different embryonic stages (oocyte, one-cell, two- to four-cell embryos).
  • Investigating the effect of mRNA injection on enhancer activity.

    • Main Results:

    • Enhancers failed to stimulate promoters in mouse oocytes and one-cell embryos, despite promoter repression.
    • Enhancer function was not restored by providing known sequence-specific enhancer-binding proteins.
    • A unique coactivator activity, absent in oocytes and one-cell embryos, was identified as essential for enhancer function starting in two- to four-cell embryos.
    • Enhancer competition was observed in two- to four-cell embryos but not in one-cell embryos.
    • mRNA from active cells partially restored enhancer function in oocytes, but not in later-stage embryos.

    Conclusions:

    • Enhancer function during early mouse development is dependent on a specific coactivator activity that is acquired during zygotic genome activation.
    • The emergence of this coactivator coincides with the onset of major zygotic gene expression.
    • Developmental stage-specific factors critically regulate the ability of enhancers to activate gene expression in vivo.