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Article Dans Une Revue Cell Reports Année : 2022

Histone marks regulate the epithelial-to-mesenchymal transition via alternative splicing

Alexandre Segelle
Andrew Oldfield
Philipp Voigt
Reini Luco

Résumé

Histone modifications impact final splicing decisions. However, there is little evidence of the driving role of these marks in inducing cell-specific splicing changes. Using CRISPR epigenome editing tools, we show in an epithelial-to-mesenchymal cell reprogramming system (epithelial-to-mesenchymal transition [EMT]) that a single change in H3K27ac or H3K27me3 levels right at the alternatively spliced exon is necessary and sufficient to induce a splicing change capable of recapitulating important aspects of EMT, such as cell motility and invasiveness. This histone-mark-dependent splicing effect is highly dynamic and mediated by direct recruitment of the splicing regulator PTB to its RNA binding sites. These results support a role for H3K27 marks in inducing a change in the cell's phenotype via regulation of alternative splicing. We propose the dynamic nature of chromatin as a rapid and reversible mechanism to coordinate the splicing response to cell-extrinsic cues, such as induction of EMT.
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hal-03681136 , version 1 (30-05-2022)

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Alexandre Segelle, Yaiza Núñez-Álvarez, Andrew Oldfield, Kimberly Webb, Philipp Voigt, et al.. Histone marks regulate the epithelial-to-mesenchymal transition via alternative splicing. Cell Reports, 2022, 38 (7), pp.110357. ⟨10.1016/j.celrep.2022.110357⟩. ⟨hal-03681136⟩
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