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Mechanism and Scaling of Eukaryotic Transcription Activation

Citation

Quintero Cadena, Porfirio (2020) Mechanism and Scaling of Eukaryotic Transcription Activation. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/m21w-8461. https://resolver.caltech.edu/CaltechTHESIS:07072020-154545363

Abstract

Transcription activation is a universal process by which living cells adapt. Decades of work in this field have produced an intelligible paradigm of transcription activation that provides fundamental insights into its underlying molecular mechanisms. This thesis attempts to extend such paradigm to explain how transcription activation can be implemented across the diversity of molecular environments found in eukaryotic nuclei. Specifically, this diversity calls for an explanation of how this process scales throughout a range of genome sizes that spans five orders of magnitude, and of how to think about this subject in the increasingly relevant context of liquid-liquid phase-separation. We leverage data from RNA-seq, smFISH, growth-rate, fluorescence microscopy, computer simulations and literature to identify an appropriate and useful level of abstraction in which to grow our current paradigm. We propose scaling and phase-separation, two seemingly disparate aspects of transcription, are explained and intrinsically linked by a novel molecular state in which multiple RNA polymerases can bind the transcription complex. We provide support and rationale for this addition to the transcription model, and generate testable hypotheses that may further clarify the mechanism and evolution of eukaryotic transcription activation.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Transcriptional bursting, RNA Pol II, CTD length, phase separation, transcription scaling
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Sternberg, Paul W.
Thesis Committee:
  • Rothenberg, Ellen V. (chair)
  • Guttman, Mitchell
  • Thomson, Matthew
  • Sternberg, Paul W.
Defense Date:15 May 2020
Non-Caltech Author Email:porfirioqc (AT) gmail.com
Funders:
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Gordon Ross Medical FoundationUNSPECIFIED
Benjamin Rosen FoundationUNSPECIFIED
Record Number:CaltechTHESIS:07072020-154545363
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:07072020-154545363
DOI:10.7907/m21w-8461
Related URLs:
URLURL TypeDescription
https://doi.org/10.1534/g3.116.036228DOIArticle adapted for Chapter 2
https://doi.org/10.1016/j.molcel.2020.05.030DOIArticle adapted for Chapter 3
ORCID:
AuthorORCID
Quintero Cadena, Porfirio0000-0003-0067-5844
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:13837
Collection:CaltechTHESIS
Deposited By: Porfirio Quintero Cadena
Deposited On:09 Jul 2020 17:11
Last Modified:17 Jul 2020 15:56

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