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

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Thesis

Year dc:date.available

2025

Author dc:creator

• Duba, Irene

Contributors dc:contributor

• Viviana I. Risca

• linker histone H1
• chromatin structure
• genome organization
• transcriptional regulation
• chromatin accessibility
• epigenetic landscape
• Life Sciences

Repository record dc:identifier

https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/799

OAI identifier oai:identifier

oai:digitalcommons.rockefeller.edu:student_theses_and_dissertations-1803