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  • The Snail repressor recruits EZH2 to specific genomic sites through the enrollment of the lncRNA HOTAIR in epithelial-to-mesenchymal transition.

The Snail repressor recruits EZH2 to specific genomic sites through the enrollment of the lncRNA HOTAIR in epithelial-to-mesenchymal transition.

Oncogene (2016-07-28)
C Battistelli, C Cicchini, L Santangelo, A Tramontano, L Grassi, F J Gonzalez, V de Nonno, G Grassi, L Amicone, M Tripodi
ABSTRACT

The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks. The Snail-repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate an lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Normal Rabbit IgG, Normal Rabbit IgG Polyclonal Antibody control validated for use in Immunoprecipitation & Western Blotting.
Sigma-Aldrich
Anti-trimethyl-Histone H3 (Lys27) Antibody, Upstate®, from rabbit
Sigma-Aldrich
Anti-EZH2 Antibody, clone BD43, clone BD43, from mouse
Sigma-Aldrich
DAPI, Dihydrochloride, Cell-permeable DNA-binding dye.