Interaction Of HPygopus2 NHD Domain With HMT Complexes

Wnt signalling pathway plays a signifficant role in determining cell fate and cell growth,differentiation,apoptosis,which is also very important during the normal tissue development or tumorigenesis.In canonical Wnt pathway,the key effector isβ-catenin,which is transported into nucleus and binds with TCF,recruiting many transcription factor and finally regulating the target gene expression.Lots of studies show thatβ-catenin can recruit some HMT complexes and such interaction is the basic activation mechanism of Wnt target gene transcription.As the dense chromatin folding of the genome does not allow the access of these sites by the huge multiprotein transcription machinery,remodelling is required to loosen up the chromatin structure for successful transcription initiation.After we got the TAP result, which showed that hPygopus2 can bind with many H3K4 HMT complexes,including the HMT complex components of WDR5,RbBP5,ASH2L,MLL2,Menin,and the binding site is included in 1-47 amino acids of NHD domain.We confirmed the interactions between hPygopus2 NHD domain and these components by co-immunoprecipitation,Western Blotting and RNA interference.And hPygopus2 NHD domain can interact with H3K4Me2 and H3K4Me3.Therefore I can make conclusion that hPygopus2 NHD domain is involved in the recruitment of the HMT components in Wnt signaling pathway,and the novel function of NHD domain may be essential for the target gene transcription of Wnt signaling pathway.