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Regulation of epigenetic signaling by subcellular localization of cofactor biosynthesis. The SAM biosynthetic enzyme MAT associates with transcription factors at specific genomic loci, producing SAM that is used by KMT enzymes to methylate histones and establish a repressive heterochromatin state. Notably, addition of exogenous SAM does not stimulate the same effect, suggesting genomic-localized biosynthesis of SAM is required for transcriptional repression.
