Dissecting the Architectural Properties of Chromatin and the Influence of the H1 Linker Histone on Chromatin Regulation

In this research, I used an existing coarse-grained chromatin model from the Collepardo Lab to study the binding of the H1 linker histone to chromatin and delve into the intrinsic properties of chromatin that regulate its architecture. The primary aim is to decipher the factors modulating chromatin organisation using a chemically-specific molecular model. I first analysed chromatin’s architecture in relation to nucleosome repeat lengths and salt concentration. A key distinction between chromatin structures with DNA linker lengths of 10n and 10n + 5 base pairs is the uniquely ordered zig-zag conformation in specific 10n systems. Consistent with the paramount physicochemical diversity of chromatin and the paradigm of phase separation, the organisation of chromatin inside the nucleus, from the nanoscale to the whole nucleus scale, has been shown to be highly heterogenous and dynamic. At the nanoscale, the heterogenous behaviour of chromatin is termed “liquid-like”. I explore how local organisation of chromatin results in liquid-like chromatin behaviour. The next section of my work explores the function of the H1 linker histone and its impact on nucleosomal interactions governing chromatin structural fluctuations. The study explores H1’s interaction with mononucleosomes, elucidating the roles of core histone tails in defining H1 mobility and illustrating how H1 governs chromatin architecture under varying conditions. I also examine the effect of different H1 variants on chromatin architecture. In collaboration with Professor Kazushiro Maeshima at the National Institute of Genetics, I further studied H1 mobility in H1 and HMGA1-rich settings. Through advanced modelling techniques and multi-disciplinary collaborations, my research provides a valuable contribution to the field of chromatin biology and beyond. My findings could have profound implications for our understanding of life at the molecular level, opening up new avenues of inquiry and potential applications in biotechnology and medicine.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2024

Author dc:creator

• Phillips, Charles

Advisor dc:contributor.advisor

• Collepardo, Rosana

• Computational
• DNA
• H1 linker histone
• Histones
• HMGA1
• Molecular Dynamics
• Replica Exchange

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/43919244-31be-41fd-9c63-926b22b94d15/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

Author Identifier

0000-0002-1417-842X

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/374502