Wingless Signaling Induces Widespread Chromatin Remodeling of Target Loci

Abstract

To package a cell's genetic material into the relatively small space provided by nuclei, linear DNA molecules are tightly wrapped around histone proteins, forming nucleosomes that are then packed together to form a higher-order structure called chromatin. This highly compacted DNA-protein assembly efficiently packages DNA but also acts as a steric barrier to transcription factors and other proteins that need to access generegulatory regions (45).

Wnt Signaling from Development to Disease: Insights from Model Systems

“…5) (Feng et al 2003;Kioussi et al 2002;Sierra et al 2006), consistent with correlation between histone acetylation and gene activation (Grewal and Moazed 2003;Robyr et al 2002). Increased H3 and H4 acetylation was also observed in fly cells, but here the increase was observed over the entire target gene, up to 30 kB away from the WREs (Parker et al 2008). This increased histone acetylation still occurred when transcription was blocked, but was dependent on CBP.…”

“…This increased histone acetylation still occurred when transcription was blocked, but was dependent on CBP. Interestingly, CBP histone acetyltransferase was restricted to the WRE (Parker et al 2008). The purpose of widespread histone acetylation is not clear, though it appears to be needed to displace ACF1, which is broadly distributed across silenced Wnt targets .…”

A role of Pygopus as an anti-repressor in facilitating Wnt-dependent transcription

“…5) is consistent with the idea that Groucho may hinder the access of Armadillo to dTCF target genes by recruiting histone deacetylases (11,12), which results in a compact chromatin structure (21)(22)(23). Loss of Groucho from dTCF target genes might lead to localized chromatin remodeling and histone acetylation (47), which may thus allow Armadillounassisted (i.e., Pygo-independent) access. Note that Armadillo itself can recruit cAMP response element-binding protein-binding protein histone acetyltransferase (48), so it could facilitate its own access to dTCF target genes by keeping their chromatin acetylated and loose (47).…”

“…For cuticle preparations and immunostaining of paraformaldehyde-fixed embryos and imaginal discs standard protocols were followed (24,47). Staining of polytene chromosomes was done as described (36).…”

“…Loss of Groucho from dTCF target genes might lead to localized chromatin remodeling and histone acetylation (47), which may thus allow Armadillounassisted (i.e., Pygo-independent) access. Note that Armadillo itself can recruit cAMP response element-binding protein-binding protein histone acetyltransferase (48), so it could facilitate its own access to dTCF target genes by keeping their chromatin acetylated and loose (47). Intriguingly, the other two Wingless antagonists we have examined that allow Pygo bypass-Brinker and Sad-have also been linked to histone deacetylases (49,50).…”