dc.contributor.advisor | Hiebert, Scott | |
dc.creator | Bomber, Monica Lorraine | |
dc.date.accessioned | 2023-01-30T22:09:29Z | |
dc.date.available | 2023-01-30T22:09:29Z | |
dc.date.created | 2023-05 | |
dc.date.issued | 2023-01-30 | |
dc.date.submitted | May 2023 | |
dc.identifier.uri | http://hdl.handle.net/1803/17962 | |
dc.description.abstract | Genetic models suggested that SMARCA5 was required for DNA templated events including transcription, DNA replication and DNA repair. We engineered a degron tag into the endogenous alleles of SMARCA5, a catalytic component of the imitation switch complexes, in three different human cell lines to define the effects of rapid degradation of this key regulator. Degradation of SMARCA5 was associated with a rapid increase in global nucleosome repeat length, which may allow greater chromatin compaction. However, there were few changes in nascent transcription within the first 6hr of degradation. Nevertheless, we demonstrated a requirement for SMARCA5 to control nucleosome repeat length at G1/S and during the S phase. SMARCA5 co-localized with CTCF and H2A.Z, and we found a rapid loss of CTCF DNA binding and disruption of nucleosomal phasing around CTCF binding sites. This spatiotemporal analysis indicates that SMARCA5 is continuously required for maintaining nucleosomal spacing. | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en | |
dc.subject | SMARCA5, PRO-seq, MNase-seq, ATAC-seq, nucleosome repeat length, CTCF, H2A.Z, chromatin, dTAG, PROTAC | |
dc.title | The role of human SMARCA5 in chromatin structure and function | |
dc.type | Thesis | |
dc.date.updated | 2023-01-30T22:09:29Z | |
dc.type.material | text | |
thesis.degree.name | PhD | |
thesis.degree.level | Doctoral | |
thesis.degree.discipline | Biochemistry | |
thesis.degree.grantor | Vanderbilt University Graduate School | |
dc.creator.orcid | 0000-0002-9489-4484 | |
dc.contributor.committeeChair | Carter, Bruce | |