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Model for how SETD2 represses tumorigenesis through multiple mechanisms. SETD2’s function can be affected in cancer through direct mutations in the SETD2 gene, or by mutations in H3.3 or deregulated expression of the demethylase KDM4A. SETD2 likely suppresses tumor formation not only through H3K36me3 but also through non-histone substrates such as α-tubulin
