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Dynamic incorporation of histone H3 variants into chromatin is essential for acquisition of aggressive traits and metastatic colonization

ABSTRACT: Carcinomas can acquire metastatic potential by undergoing a cellular program referred to as epithelial-to-mesenchymal transition (EMT). During EMT, the genome undergoes major epigenetic changes required for the expression of genes that promote cell motility, invasiveness, and survival under stress. While recent data point to a crucial role of chromatin remodeling in this process, little is known about the nature of this remodeling and the signals that trigger it. Here we show that metastasis-inducing pathways regulate histone chaperones to reduce canonical histone incorporation into chromatin. This triggers deposition of H3.3 to the promoters of EMT-inducing transcription factors and poor prognosis genes, a phenomenon that is sufficient and necessary for the induction of EMT and metastasis. Together, we have discovered histone H3.3 variant as a major regulator of cell fate during tumorigenesis and histone chaperones as valuable therapeutic targets for metastatic disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE119030 | GEO | 2019/09/02

REPOSITORIES: GEO

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Dynamic incorporation of histone H3 variants into chromatin is essential for acquisition of aggressive traits and metastatic colonization

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