Abstract

The activity of a transcription factor (TF) can be remarkably heterogeneous, both within andbetween cells. Between cells, molecular fluctuations drive stochastic differences in the activitiesof TFs. I will describe a project in which we have quantified how the different components of aTF (its activation domain, affinity for DNA, concentration, and cooperative interactions) influencestochastic fluctuations in TF activity. In addition to stochastic fluctuations between cells, withincells TFs can switch between activating and repressing activities depending on the cis-regulatorycontent of their target genes. I will describe a second project in which we have modelled howthe balance between homo- and heterotypic interactions determines whether a TF will function asan activator or repressor. Understanding and quantitatively modeling the factors underlying TFheterogeneity will be necessary if we are to predict patterns of gene expression from cis-regulatoryDNA. Our work suggests that biophysically-informed models will be an important part of capturingthe context-specific activities of TFs.

Committee Chair

Barak Cohen

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Computational & Systems Biology)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

8-3-2023

Language

English (en)

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