Methyllysine (KMe) histone �marks� constitute a critical component of the epigenetic code that determines development and differentiation. Multiple proteins were identified as �readers� of the methyllysine code. The KMe �readers� feature a phenomenal plasticity enabling them to selectively recognize methylation states that, through a series of protein-protein interactions, results in massive gene silencing. Understanding the biophysics of this plasticity would enable rational therapeutic approaches to epigenetic disorders. Here, we report our recent results on energetics and dynamics of the KMe histone code at two contiguous levels: (i) a selective recognition of various methylation states by their cognate �readers�; and (ii) structural changes in reader proteins upon KMe binding. We applied multiple computational and experimental approaches including Molecular Dynamics, site-directed mutagenesis, small-molecule probes, GFP-fusion localization and some others. The resulting biophysical models were successfully used to design more efficient chemical probes and helped to reveal an intriguing allosterism in KMe �reading�.

Elucidating the enigmatic plasticity of histone-methyllysine-code readers

243rd National Meeting (2012)

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