Snail2–PHD12 interaction recruits an epigenetic repressive complex that mediates neural crest epithelial–mesenchymal transition

STROBL MAZZULLA, P.H.; BRONNER-FRASER, M.

Chicago, Ilinois

Congreso; Society for Developmental Biology 70TH Annual Meeting; 2011

Society for Developmental Biology

The epithelial to mesenchymal transition (EMT) is a process by which epithelial cells are converted from a tightly adherent sheet of cells into a more dispersed mesenchymal population. Neural Crest (NC) cells are a transient pluripotent cell population that delaminate from the dorsal neural tube via an EMT, migrate extensively and contribute to numerous derivatives. It is well-known that Snail represses cadherin expression, guiding changes in the adhesion properties prior NC EMT. However, the molecular mechanisms underlying its repressive activity were unknown. Here, we characterize a Plant-Homeodomain factor (PHD12) that we show interacts with both Snail2 and the Sin3A/HDAC repressive complex using an in vivo immunoprecipitacion assay. PHD12 knock-down embryos were used for a multiplex Nanostring expression analysis, evidencing an elevated Cadherin6b (Cad6b) and low NC specifier makers (Sox10, FoxD3, Snail2) in the dorsal neural tube after loss of PHD12. These results were validated by immunohistochemistry using specific antibodies showing lack of migrating NC together with an increase in Cad6b expression at the dorsal aspect of the neural tube. Using an in vivo chromatin immunoprecipitation assay we provides evidence that PHD12 protein interacts with the Cad6b locus only prior NC migration, concomitantly with promoter hypoacetylation. Taken together, we provide the first in vivo evidence showing the molecular mechanism of Snail2 repression via association with an epigenetic repressive complex that deacetylates the promoter of a target gene, Cad6b.