Solid-state NMR studies of chromatin structure and dynamics

Understanding the dynamic organization of chromatin is indispensable as it provides crucial information to delineate cellular processes that it mediates–DNA replication, transcription, and repair. Nucleosome core particle (NCP) composed of core histones, organizing ~147 bp of DNA constitutes the fun...

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Main Author: Prasanna, Chinmayi
Other Authors: Lars Nordenskiöld
Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2021
Subjects:
Online Access:https://hdl.handle.net/10356/146519
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author Prasanna, Chinmayi
author2 Lars Nordenskiöld
author_facet Lars Nordenskiöld
Prasanna, Chinmayi
author_sort Prasanna, Chinmayi
collection NTU
description Understanding the dynamic organization of chromatin is indispensable as it provides crucial information to delineate cellular processes that it mediates–DNA replication, transcription, and repair. Nucleosome core particle (NCP) composed of core histones, organizing ~147 bp of DNA constitutes the fundamental unit of eukaryotic chromatin. While the structure of nucleosome is investigated predominantly using X-ray crystallography, quantitative information about nucleosome dynamics remains elusive. Our objective is to address this gap using solid-state nuclear magnetic resonance (SSNMR) spectroscopy, which is a state-of-the-art technology to probe protein dynamics at atomic resolution. We have conducted SSNMR experiments for human histones in the NCP at physiological chromatin concentrations to probe the site-specific motions and amplitudes. We also investigated the influence of histone dynamics in the context of nucleosomes in the chromatin fiber and the human telomeric repeat DNA sequence. Our study is the first to have probed quantitative motions of histones in the chromatin.
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spelling ntu-10356/1465192023-02-28T18:43:23Z Solid-state NMR studies of chromatin structure and dynamics Prasanna, Chinmayi Lars Nordenskiöld School of Biological Sciences LarsNor@ntu.edu.sg Science::Biological sciences Understanding the dynamic organization of chromatin is indispensable as it provides crucial information to delineate cellular processes that it mediates–DNA replication, transcription, and repair. Nucleosome core particle (NCP) composed of core histones, organizing ~147 bp of DNA constitutes the fundamental unit of eukaryotic chromatin. While the structure of nucleosome is investigated predominantly using X-ray crystallography, quantitative information about nucleosome dynamics remains elusive. Our objective is to address this gap using solid-state nuclear magnetic resonance (SSNMR) spectroscopy, which is a state-of-the-art technology to probe protein dynamics at atomic resolution. We have conducted SSNMR experiments for human histones in the NCP at physiological chromatin concentrations to probe the site-specific motions and amplitudes. We also investigated the influence of histone dynamics in the context of nucleosomes in the chromatin fiber and the human telomeric repeat DNA sequence. Our study is the first to have probed quantitative motions of histones in the chromatin. Doctor of Philosophy 2021-02-23T05:40:53Z 2021-02-23T05:40:53Z 2020 Thesis-Doctor of Philosophy Prasanna, C. (2020). Solid-state NMR studies of chromatin structure and dynamics. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/146519 10.32657/10356/146519 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University
spellingShingle Science::Biological sciences
Prasanna, Chinmayi
Solid-state NMR studies of chromatin structure and dynamics
title Solid-state NMR studies of chromatin structure and dynamics
title_full Solid-state NMR studies of chromatin structure and dynamics
title_fullStr Solid-state NMR studies of chromatin structure and dynamics
title_full_unstemmed Solid-state NMR studies of chromatin structure and dynamics
title_short Solid-state NMR studies of chromatin structure and dynamics
title_sort solid state nmr studies of chromatin structure and dynamics
topic Science::Biological sciences
url https://hdl.handle.net/10356/146519
work_keys_str_mv AT prasannachinmayi solidstatenmrstudiesofchromatinstructureanddynamics