Fig. 9

H2A.Z is an effector of the Wnt pathway on differentiation markers. a Caco-2/15 were treated using siRNA targeting β-catenin mRNA or control and transfected with vectors encoding or not H2A.Z to analyse the impact of H2A.Z forced expression on the effects of β-catenin knockdown. The expression of the indicated genes was measured for each condition (calculated relative to β2 M and RPLP0 (p0) mRNA levels). The mean and standard error are shown (n = 6 independent experiments). Statistical analysis was done using Student’s t-Test (*p < 0.05; **p < 0.02 vs β-catenin siRNA + empty vector condition). b Same as in a for Wnt target genes. c Working model: in our study, we showed that the Wnt/β-catenin/TCF7L2(TCF4) signaling pathway positively regulates the expression of the H2A.Z histone variant. The incorporation of the variant, mediated by chromatin modifying complexes, is then increased and responsible for the low recruitment of the intestine-specific transcription factor CDX2 on its target genes and thus, limits the expression of such genes. Since it is known that H2A.Z occupancy of a specific promoter is a signature for intestinal stem cells and that this enrichment is reduced upon differentiation, our data show that H2A.Z participates in the regulation of epithelial differentiation through Wnt signaling. Thus, our study demonstrates that a structural chromatin mark can control the cell fate of normal progenitors and, thereafter, intestinal epithelial homeostasis