Poster abstracts

Poster number 5 submitted by Wenjun Sun

NMR Studies of Conformation, Dynamics, and Interaction of Histone Tail Domains in Nucleosomes

Wenjun Sun (Department of Chemistry and Biochemistry, The Ohio State University ), Olga O. Lebedenko (Laboratory of Biomolecular NMR, St. Petersburg State University), Nicole Gonzalez Salguero, Mohamad Zandian, Vidhyalakshmi Sridharan (Department of Chemistry and Biochemistry, The Ohio State University ), Michael G. Poirier (Department of Physics, The Ohio State University), Nikolai R. Skrynnikov (Laboratory of Biomolecular NMR, St. Petersburg State University; Department of Chemistry, Purdue University), Christopher P. Jaroniec (Department of Chemistry and Biochemistry, The Ohio State University )

Abstract:
The fundamental unit of chromatin, the nucleosome, which is composed of ~147 bp DNA and a histone protein octamer complex containing two copies each of core histones H2A, H2B, H3 and H4. Dynamically disordered H3 and H4 N-terminal tails are key components in chromatin regulation and compaction. Previously, 15N NMR relaxation rates coupled with microsecond time-scale molecular dynamics (MD) simulations for histone H4 tail indicated that histone H4 tails form a fuzzy interaction with nucleosomal DNA1. In this study, we investigate the conformational ensembles and interactions of the H4 tail in nucleosomes by solution NMR measurements of paramagnetic relaxation enhancements (PREs) combined with microsecond time-scale MD simulations of the nucleosome core particle. The PRE data reports on proximities between spin labels in H3 positions: K36C, L65C, K79C, Q125C and H4 N-terminal tail residues. Collectively, these data enable improved location of the H4 tails and support the notion that H4 tails engage in a fuzzy-complex interaction with nucleosomal DNA2. Here we further extend our studies in conformation, dynamics, and interaction of H3 and H4 histone tails in nucleosomes. Specially, we report residue-specific dynamic information of these tail domains in reconstituted nucleosomes as a function of ionic strength, and histone protein reader binding by the measurements of 15N relaxation rates. Overall, the relaxation data shows that histone tails in nucleosomes are modulated by these effects.

References:
1. Rabdano, Sevastyan O et al. “Histone H4 Tails in Nucleosomes: a Fuzzy Interaction with DNA.” Angewandte Chemie (International ed. in English) vol. 60,12 (2021): 6480-6487. doi:10.1002/anie.202012046
2. Sun, Wenjun et al. “Conformational and Interaction Landscape of Histone H4 Tails in Nucleosomes Probed by Paramagnetic NMR Spectroscopy.” Journal of the American Chemical Society vol. 145,46 (2023): 25478-25485. doi:10.1021/jacs.3c10340

Keywords: Histone tail, NMR, Dynamics