A number of SET1-type complex proteins are pulled down from HeLa and SW480 extracts by a fragment of beta-catenin consisting of ARM repeats 11 and 12 and the adjacent C-terminal activation domain (Sierra et al, 2006). SET1 complexes are histone methyltransferases that promote H3K4 trimethylation in a manner that depends on prior ubiquitination of H2B; H3K4 is a mark associated with active chromatin (reviewed in Shilatifard, 2006). ChIP experiments show that SET1 complex members MLL2, MEN1, RBBP5 and ASH2L cycle on and off the MYC promoter in vivo in a complex with BCL9, PYGO and beta-catenin. Recruitment of the SET proteins correlates with increased H3K4me3 and transcription of the MYC gene, and endogenous mMYC mRNA levels decline somewhat in the presence of MLL2 siRNA. These data suggest that the C-terminal of beta-catenin interacts with a functional histone H3 methyltransferase complex that activates WNT-target gene transcription (Sierra et al, 2006).