Bernhardt, ThomasGibson, Jacob2022-06-0720222022-05-162022-05Gibson, Jacob. 2022. The role of the membrane in directing transcription: the regulation and functional implications of CRP membrane association. Doctoral dissertation, Harvard University Graduate School of Arts and Sciences.29209409https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37372166The cyclic AMP receptor protein (CRP) is a highly conserved global transcription factor that has long served as a model for the study of transcriptional mechanisms in bacteria. Here, I provide evidence of a novel regulatory mechanism for CRP in Vibrio cholerae. In particular, I provide evidence that, under certain environmental conditions, CRP is conditionally associated with the cytoplasmic membrane as part of a mechanism necessary for its activity at a subset of its regulon. This membrane association is dependent on the presence of a histone-like protein, PepA, which I identified as a novel membrane-associated interaction partner for CRP. I also identified a set of positive residues necessary for the interaction of CRP with PepA and present evidence that this interaction is prevented by post-translational modification of these residues. I propose that reversible post-translational modification of CRP under certain environmental signals regulates an interaction between CRP and PepA at the membrane that is required to facilitate CRP activity at a subset of promoters.application/pdfenMicrobiologyBiologyThesis or Dissertation2022-06-070000-0002-7493-3722