For FY16, we have used multi-dimensional NMR, X-ray crystallography, site-directed mutagenesis coupled with isothermal titration calorimetry to study how nucleosomes and histones are recognized by other proteins. We have determined the crystal structure of the chromatosome containing the globular domain of H5 and identified two different binding modes of linker histones, which have implications for the higher-order chromatin structures. We further obtained a new crystal structure of the chromatosome whose packing in the crystal suggests a ladder-like chromatin structure.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010808-10
Application #
9343708
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Zhou, Bing-Rui; Jiang, Jiansheng; Ghirlando, Rodolfo et al. (2018) Revisit of Reconstituted 30-nm Nucleosome Arrays Reveals an Ensemble of Dynamic Structures. J Mol Biol 430:3093-3110
Chittori, Sagar; Hong, Jingjun; Saunders, Hayden et al. (2018) Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N. Science 359:339-343
Fyodorov, Dmitry V; Zhou, Bing-Rui; Skoultchi, Arthur I et al. (2018) Emerging roles of linker histones in regulating chromatin structure and function. Nat Rev Mol Cell Biol 19:192-206
Liu, Chuanbo; Wang, Tianshu; Bai, Yawen et al. (2017) Electrostatic forces govern the binding mechanism of intrinsically disordered histone chaperones. PLoS One 12:e0178405
Zhou, Bing-Rui; Feng, Hanqiao; Ghirlando, Rodolfo et al. (2016) A Small Number of Residues Can Determine if Linker Histones Are Bound On or Off Dyad in the Chromatosome. J Mol Biol 428:3948-3959
Zhou, Bing-Rui; Jiang, Jiansheng; Feng, Hanqiao et al. (2015) Structural Mechanisms of Nucleosome Recognition by Linker Histones. Mol Cell 59:628-38
Hong, Jingjun; Feng, Hanqiao; Wang, Feng et al. (2014) The catalytic subunit of the SWR1 remodeler is a histone chaperone for the H2A.Z-H2B dimer. Mol Cell 53:498-505
Hong, Jingjun; Feng, Hanqiao; Zhou, Zheng et al. (2013) Identification of functionally conserved regions in the structure of the chaperone/CenH3/H4 complex. J Mol Biol 425:536-45
Kato, Hidenori; Jiang, Jiansheng; Zhou, Bing-Rui et al. (2013) A conserved mechanism for centromeric nucleosome recognition by centromere protein CENP-C. Science 340:1110-3
Zhou, Bing-Rui; Feng, Hanqiao; Ghirlando, Rodolfo et al. (2012) Histone H4 K16Q mutation, an acetylation mimic, causes structural disorder of its N-terminal basic patch in the nucleosome. J Mol Biol 421:30-7

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