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Drug platforms

Locus-specific control of histone modification using transcription activator-like (TAL) effector repeat fusion proteins

TAL effector repeats linked to chromatin-modifying enzymes could enable locus-specific chromatin modification and inform epigenetic drug development. TAL effector repeats targeting specific DNA sequences were linked to lysine-specific histone demethylase 1 (KDM1A; LSD1), which enabled locus-specific binding and reduction in levels of H3K4me2 and H3K27 acetylation, whereas a TAL effector alone did not. Next steps include using this approach to better understand how compounds that inhibit chromatin-modifying proteins function in normal and cancerous cells and to guide their development and identify potential biomarkers.

SciBX 6(38); doi:10.1038/scibx.2013.1079
Published online Oct. 3, 2013

Patent application filed; available for licensing

Mendenhall, E.M. et al. Nat. Biotechnol.; published online Sept. 8, 2013;
doi:10.1038/nbt.2701
Contact: Bradley E. Bernstein, Massachusetts General Hospital, Boston, Mass.
e-mail:
bernstein.bradley@mgh.harvard.edu