Regulation of Chromatin Multi-Scale Organization and Function by Linker Histone H1

Author

Irene Duba

Date of Award

2024

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Thesis Advisor

Viviana I. Risca

Abstract

The three-dimensional organization of the genome is critical for regulating gene expression and maintaining cellular identity. The organizing principles underlying this 3D structure are a subject of much study, and it has proven to be a complex system to unravel. There are multiple scales of genome organization, ranging from single basepair modifications to chromatin compartments spanning many megabasepairs, and innumerable factors influence and regulate genome structure and function. One factor that appears to play a key role is linker histone H1, which is the most prevalent chromatin-binding protein in the cell. It has long been thought to be responsible for compacting chromatin and repressing transcription, though many historical studies of H1 were performed in vitro, and the details of its role in cells remain unclear. H1 is essential in mammals, and stable depletion in cells has previously resulted in disruption of higher-order chromatin structure, epigenetic landscape, and, to varying degrees, gene regulation. Here, we show that acute H1 depletion results in decompaction of the chromatin fiber, accompanied by transcriptional derepression and increased chromatin accessibility. In contrast to stable H1 knockdown, long-range chromatin structure and the epigenetic landscape are only modestly affected in our acute depletion system, indicating that these are downstream effects of H1 depletion. These findings show that the primary function of H1 in cells is influencing short-range chromatin structure and transcription, and further unravel the relationship between genome structure and function by showing that major gene regulation can occur without strong shifts in the epigenetic landscape or long-range chromatin organization.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

Recommended Citation

Duba, Irene, "Regulation of Chromatin Multi-Scale Organization and Function by Linker Histone H1" (2024). Student Theses and Dissertations. 799.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/799