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University of Rochester

1. Cutter, Amber Rae. Molecular Characterization of Nucleosome Recognition by Linker Histone H1.0.

Degree: PhD, 2020, University of Rochester

Linker histones (H1s) are essential components of metazoan chromatin, facilitating chromatin condensation and regulation of numerous biological processes. However, how H1 binds to nucleosomes and specifically stabilizes chromatin structures is unclear. To provide insight into its role in higher order chromatin structure, this work identifies interactions between H1 globular domain (G) and C-terminal domain (CTD) regions and nucleosomes. Using a strategy of H1 site-specific crosslinking, I mapped interactions of selected globular domain residues with nucleosome DNA to single-base resolution. This information illuminated molecular details of how the H1 globular domain achieves nucleosome structure-specific recognition, and precisely defined the binding orientation of the H1 G domain on the nucleosome. These biochemical analyses complement structural observations, and provided critical constraints for refinement of a model of the nucleosome in complex with H1. Additionally, I investigated the mechanism by which members of the high mobility group nucleosome binding (HMGN) family counteract the propensity of H1 to stabilize formation of higher order chromatin structures, to facilitate transcription. Surprisingly, my data support that HMGNs do not displace H1s from nucleosomes; rather these proteins bind nucleosomes simultaneously with H1s without disturbing specific contacts between GH1 and nucleosomal DNA. Finally, I report the first set of specific contacts identified between the H1 CTD and linker DNA, providing key insights into the role of the H1 CTD in DNA charge neutralization and compaction. To further characterize the chromatin condensation functions of H1, interactions between H1 and oligonucleosome arrays were also studied. Taken together, this work advances our understanding of nucleosome recognition by H1 and will inform future efforts to understand the mechanism for assembly of higher-order chromatin structures.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Cutter, A. R. (2020). Molecular Characterization of Nucleosome Recognition by Linker Histone H1.0. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/35519

Chicago Manual of Style (16th Edition):

Cutter, Amber Rae. “Molecular Characterization of Nucleosome Recognition by Linker Histone H1.0.” 2020. Doctoral Dissertation, University of Rochester. Accessed April 09, 2020. http://hdl.handle.net/1802/35519.

MLA Handbook (7th Edition):

Cutter, Amber Rae. “Molecular Characterization of Nucleosome Recognition by Linker Histone H1.0.” 2020. Web. 09 Apr 2020.

Vancouver:

Cutter AR. Molecular Characterization of Nucleosome Recognition by Linker Histone H1.0. [Internet] [Doctoral dissertation]. University of Rochester; 2020. [cited 2020 Apr 09]. Available from: http://hdl.handle.net/1802/35519.

Council of Science Editors:

Cutter AR. Molecular Characterization of Nucleosome Recognition by Linker Histone H1.0. [Doctoral Dissertation]. University of Rochester; 2020. Available from: http://hdl.handle.net/1802/35519

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