Erratum: Regulation of cancer epigenomes with a histonebinding synthetic transcription factor

Abstract

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Tandem histone-binding domains enhance the activity of a synthetic chromatin effector

“…The CBX8 effector protein binds to histone H3 trimethylated at lysine 27 (H3K27me3) through its Nterminal Polycomb chromodomain (PCD) and establishes a silenced transcriptional state. Expression of PcTF, an artificial transcriptional activator with an Nterminal PCD, mCherry tag, and Cterminal VP64 activation domain, led to increased expression of H3K27me3enriched genes in three different cancerderived cell lines [10,11] . These results show promise for designing transcription factors that can read chromatin marks to rewire aberrant epigenetic programming.…”

“…In other work, we observed stronger gene upregulation when mCherryVP64 was targeted to a promoter via a Gal4 DNA binding domain compared to the PCD histone binding domain [18] . PcTFmediated gene activation is dosedependent [11] , and high PcTF expression levels are required for optimal activity. This limits the usefulness of PcTF for therapeutic applications where barriers to delivery severely limits the number of proteins that ultimately reach the nuclei of target cells.…”