The Pygo2-H3K4me2/3 interaction is dispensable for mouse development and Wnt signaling-dependent transcription

Development. 2013 Jun;140(11):2377-86. doi: 10.1242/dev.093591. Epub 2013 May 1.


Pygopus has been discovered as a fundamental Wnt signaling component in Drosophila. The mouse genome encodes two Pygopus homologs, Pygo1 and Pygo2. They serve as context-dependent β-catenin coactivators, with Pygo2 playing the more important role. All Pygo proteins share a highly conserved plant homology domain (PHD) that allows them to bind di- and trimethylated lysine 4 of histone H3 (H3K4me2/3). Despite the structural conservation of this domain, the relevance of histone binding for the role of Pygo2 as a Wnt signaling component and as a reader of chromatin modifications remains speculative. Here we generate a knock-in mouse line, homozygous for a Pygo2 mutant defective in chromatin binding. We show that even in the absence of the potentially redundant Pygo1, Pygo2 does not require the H3K4me2/3 binding activity to sustain its function during mouse development. Indeed, during tissue homeostasis, Wnt/β-catenin-dependent transcription is largely unaffected. However, the Pygo2-chromatin interaction is relevant in testes, where, importantly, Pygo2 binds in vivo to the chromatin in a PHD-dependent manner. Its presence on regulatory regions does not affect the transcription of nearby genes; rather, it is important for the recruitment of the histone acetyltransferase Gcn5 to chromatin, consistent with a testis-specific and Wnt-unrelated role for Pygo2 as a chromatin remodeler.

Keywords: Chromatin; Drosophila; Mouse; Pygopus; Transcriptional regulation; Wnt signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin Assembly and Disassembly
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology
  • Female
  • Fertility
  • Gene Expression Regulation, Developmental*
  • Gene Knock-In Techniques
  • Genotype
  • Histones / metabolism*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Protein Interaction Domains and Motifs
  • Testis / metabolism
  • Wnt Signaling Pathway*
  • p300-CBP Transcription Factors / metabolism


  • Drosophila Proteins
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • pygo protein, Drosophila
  • pygopus 2 protein, mouse
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor