Cross-regulation of post-translational protein modifications and effects on the histone H3 tail conformations/dynamics: A structural and mechanistic study on whole nucleosomes by Nuclear Magnetic Resonance (NMR) spectroscopy.

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The aim of this study is to expand my ongoing investigation on characterizing the structural and dynamic properties of histone H3 tail and its post-translational modifications (PTMs) to a system that resembles the natural occurring chromatin fiber under different functional/condensed states. Specifically, isotope-labeled histone H3 containing distinct sets of PTMs will be used to reconstitute nucleosomal arrays that will undergo folding transitions and they will be analyzed by NMR spectroscopy. Results from these analyses will advance our understanding on the role of histone tail dynamics and their PTMs on regulating transitions between functional chromatin states Additionally, differentially isotope-labeled histones will be incorporated on nucleosomes as to investigate the interplay between the catalytic and the acetyl-lysine recognition domain of the transcriptional co-activator CBP on the regulation of its acetyltransferase activity. Understanding the molecular mechanism that controls CBP activity has implications for pharmacological targeting.