Doctoral thesis
OA Policy
English

Chromatin Remodeling: Discovery and Functional Analysis of SWI/SNF Complex Modulators

ContributorsSchwaemmle, Hannaorcid
DirectorsBraun, Simon
Number of pages174
Imprimatur date2025-10-17
Defense date2025-10-17
Abstract

The SWI/SNF complex is an essential nucleosome remodeler, which generates chromatin accessibility to control gene expression. Mutations in SWI/SNF subunits are frequent in various neurodevelopmental disorders and cancers. In this thesis, we aimed to increase our mechanistic understanding of SWI/SNF regulation and identify novel therapeutic targets for treating diseases caused by SWI/SNF mutations. First, we developed a live/dead reporter of SWI/SNF activity in mouse embryonic stem cells and performed a genome-wide CRISPR KO screen to uncover novel modulators of SWI/SNF function. Followingly, we validated three hits and uncovered the molecular mechanisms linking each novel modulator to SWI/SNF activity. First, we discovered that the m6A-writer subunit RBM15 controls stoichiometric assembly of SWI/SNF complexes. Next, we discovered that the MLF2 protein acts as a chaperone of SWI/SNF complex assembly. Finally, we found that the chromatin modifier PHF6 and SWI/SNF coregulate the expression of key neurodevelopmental genes. Overall, this study gives valuable insights into different modes of SWI/SNF regulation.

Keywords
  • Chromatin
  • Chromatin remodelling
  • Epigenetics
Citation (ISO format)
SCHWAEMMLE, Hanna. Chromatin Remodeling: Discovery and Functional Analysis of SWI/SNF Complex Modulators. Thèse, 2025. doi: 10.13097/archive-ouverte/unige:189079
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Creation21/11/2025 15:32:09
First validation24/11/2025 13:53:52
Update17/08/2026 07:18:39
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