Investigating the Molecular Mechanism of Heterochromatic Gene Silencing
The heterochromatin domain is an essential component of the eukaryotic genome, which contains many repetitive non-protein-coding sequences that must be transcriptionally silenced to maintain genomic integrity. Heterochromatic sequences from multiple chromosomes are organized into nuclear domains that concentrate heterochromatic proteins and exclude euchromatic factors. These domains prevent transcription and recombination of the sequences inside, perhaps because of the density of chromatin packing in the domain. However, this chromatin compaction model is inconsistent with other observations, including high mobility of proteins inside the heterochromatin domain. Recent studies have shown that biological phase separation can result in distinct cellular compartments without bounding membranes, which leads us to ask if phase separation is the selective mechanism that explains how the heterochromatin domain is transcriptionally silenced while maintaining mobility of internal components. To study this, I will employ single molecule tracking to directly image the path of euchromatic molecules to determine how they are excluded from the heterochromatin domain; by chromatin compaction or phase separation. If phase separation is the mechanism for heterochromatin transcriptional silencing, it suggests that basic physical principles can determine functional outcomes in the nucleus and will fundamentally shift our understanding of nuclear organization.
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- Major: Molecular and Cell Biology
- Mentor: Gary Karpen