Research – Nature – Regulation of cancer epigenomes with a histone-binding synthetic transcription factor

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Figure6_finalRegulation of cancer epigenomes with a histone-binding synthetic transcription factor.
Nyer DB, Daer R, Vargas D, Hom C, Haynes KA. (2017) Nature Genomic Medicine. http://rdcu.be/oqv7

This work expands our 2011 report in many important ways. We studied the behavior of a synthetic chromatin protein that we designed called PcTF in bone, blood, and brain cancer-derived cells. We expected to see PcTF bind to methylated histones, but instead saw strong signals closer to histone-free gene promoters. However, PcTF activity still required the methyl-histone binding domain to interact with its targets. It appears that PcTF bridges methylated histone signals with the transcription complex. We also discovered that PcTF activates a key tumor suppressor, CASZ1 as well as other silenced genes in all three cancer cell types. This new information has advanced our understanding of how a potentially therapeutic histone-binding protein behaves in cancer cells.

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