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Wingless signaling induces widespread chromatin remodeling of target loci

David S Parker1, Yunyun Y Ni, Jinhee L Chang

  • 1Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048. cadigan@umich.edu.

Molecular and Cellular Biology
|December 28, 2007
PubMed

Insights

Wingless/Wnt signaling in Drosophila induces widespread histone acetylation around target genes, independent of transcription. This chromatin modification, mediated by CBP, precedes gene activation.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Developmental Biology

Background:

  • Signaling cascades' influence on gene regulation via chromatin modification remains unclear.
  • The Wingless/Wnt pathway in Drosophila involves Armadillo (fly beta-catenin) nuclear translocation and TCF binding for gene activation.

Purpose of the Study:

  • To investigate how signaling cascades, specifically the Wingless/Wnt pathway, impact gene regulation through chromatin modification.
  • To elucidate the mechanism of localized signaling molecule recruitment and its effect on chromatin structure.

Main Methods:

  • Studied the Wingless/Wnt pathway in Drosophila.
  • Analyzed the recruitment of TCF and Armadillo to Wingless response elements.
  • Assessed histone acetylation patterns using ChIP or similar techniques.
  • Investigated the role of CBP (histone acetyltransferase) in the process.

Main Results:

  • Wingless signaling triggers localized recruitment of TCF and Armadillo to specific TCF binding site clusters (Wingless response elements).
  • Pathway activation leads to widespread histone acetylation (up to 30 kb) surrounding these elements, independent of active transcription.
  • Widespread acetylation of Wingless targets depends on CBP and correlates with target gene expression activation.

Conclusions:

  • Pathway activation results in localized recruitment of TCF/Armadillo/CBP to Wingless response elements.
  • This localized recruitment initiates widespread histone acetylation of target loci preceding transcriptional activation.
  • The findings provide insights into the interplay between signaling pathways and epigenetic regulation of gene expression.

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