The proper packaging of the genome in eukaryotic nuclei is essential for proper gene expression and cell function. Chromatin at the large scale is divided into two major compartments heterochromatin and euchromatin. Heterochromatin compromises the transcriptionally inactive tightly packaged regions of chromatin, while euchromatin is the transcriptionally active region of chromatin.
The Heterochromatin Protein family (HP1) proteins are epigenetic hallmarks of constitutive heterochromatin. Recent evidence suggests human HP1α undergoes liquid-liquid phase separation suggesting a role for HP1 phase separation in the formation of compacted heterochromatin within HP1 droplets. Phase separation is a biophysical property of proteins with intrinsically disordered domains which are protein domains that lack a defined secondary structure and have the ability to undertake multiple conformations.
In this thesis, I investigated the ability of C. elegans HP1 homologs HPL-2A and HPL-1 to phase separate utilizing directed mutations to elucidate the intermolecular interactions that govern this phenomenon and different assays to assess their phase separation.
I concluded that HPL-2A is a bona fide phase separating protein that selectively condenses chromatin. HPL-2A’s phase separation depends on specific interactions, mainly dimerization and the presence of lysine and arginine residues in the hinge region. HPL-2A has a specific IDR that drives its phase separation which is the hinge region as the CTE and NTE are not essential for its phase separation.
| Identifer | oai:union.ndltd.org:kaust.edu.sa/oai:repository.kaust.edu.sa:10754/693522 |
| Date | 09 August 2023 |
| Creators | Alotaibi, Aljoharah |
| Contributors | Fischle, Wolfgang, Biological and Environmental Science and Engineering (BESE) Division, Arold, Stefan T., Aranda, Manuel |
| Source Sets | King Abdullah University of Science and Technology |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Rights | 2024-08-09, At the time of archiving, the student author of this thesis opted to temporarily restrict access to it. The full text of this thesis will become available to the public after the expiration of the embargo on 2024-08-09. |
| Relation | N/A |
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