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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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The CAF-1 complex couples Hippo pathway target gene expression and DNA replication

William B Yee1,2, Patrick M Delaney3, Pamela J Vanderzalm1,4

  • 1Department of Molecular Genetics and Cell Biology.

Molecular Biology of the Cell
|September 26, 2019
PubMed

Insights

Nucleosome assembly by the chromatin assembly complex-1 (CAF-1) competes with Yorkie (Yki) for Hippo pathway targets. Reducing CAF-1 enhances Yki

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Genetics

Background:

  • The Hippo signaling pathway is crucial for regulating tissue growth and organ development.
  • Yorkie (Yki), a transcriptional coactivator, promotes gene expression driving growth.
  • Yki function is enhanced by chromatin modifiers that increase DNA accessibility.

Purpose of the Study:

  • To investigate if DNA replication-associated changes in chromatin accessibility affect Yki function.
  • To explore the role of the chromatin assembly complex-1 (CAF-1) in regulating Hippo pathway activity.

Main Methods:

  • Depletion of CAF-1 in the wing imaginal epithelium of Drosophila.
  • Analysis of Hippo pathway target gene expression.
  • Assessment of Yki association with target DNA sites.
  • Investigation of DNA replication dependence of target gene expression.

Main Results:

  • CAF-1 depletion increased Hippo pathway target gene expression without affecting other genes.
  • Yki exhibited increased association with target sites upon CAF-1 depletion.
  • Misregulation of target gene expression was Yki-dependent.
  • Increased target gene expression was dependent on DNA replication, with reduced nucleosome density at target sites.

Conclusions:

  • Nucleosome assembly by CAF-1 competes with Yki for binding to Hippo pathway targets post-DNA replication.
  • Cell cycle progression and Hippo pathway target expression are interconnected.
  • These findings offer insights into the Hippo pathway's role in normal and abnormal tissue growth.

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