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This lecture discusses the role of RNA polymerase as a molecular motor in transcriptional control. It explores topics such as the average step size of RNA polymerase, transcriptional regulation, and the complexity of gene control in bacteria. Additionally, it covers the lac operon and its positive and negative regulatory elements, as well as the role of transcription factors in tissue development.
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Lecture 12 RNA polymerase as a molecular motor Transcriptional control
RNA polymerase as a molecular motor from Gelles 1998
Average step size = 3.7A, which corresponds to the base spacing in B-DNA
DNA –> transcription –> RNA –> translation -> Protein The complexity and diversity of today’s forms of life are primarily due to two relatively simple types of physico-chemical phenomena: 1. Cooperative binding 2. Steric hindrance
In bacteria: Even though lactose, arabinose and other sugars may be available for the cell, in the presence of glucose the production of enzymes metabolizing sugars other than glucose is repressed. This is known as catabolite repression. lac operon contains 3 genes necessary for consumption of galactose: (1) b-galactosidase, (2) galactoside permease and (3) thiogalactoside transacetylase There are positive and negative regulatory elements that make catabolite repression work. cAMP receptor protein (CAP), acting as a homodimer can bind both cAMP and DNA. When glucose is absent (high cAMP state), CAP binds to its positive regulatory element increasing transcription of the lac operon 50-fold. Lac repressor is a tetrameric complex that in the absence of lactose binds tightly to the operator region covering the transcription initiation site. In the presence of lactose or lactose mimicking substances (IPTG) it falls off.
The Lac Operon High level of transcription takes place when glucose is low and lactose is high. Without bound activator (CAP-cAMP) the lac promoter is poorly transcribed even when lactose concentrations are high and the Lac repressor is unbound (read section 7.1 for more information on prokaryotic gene control)
Pax6 is a transcription factor responsible for development of several tissues. It utilizes 3 different promoters at distinct times during embryogenesis.
Ligand binding changes conformation of the estrogen receptor
Cooperative binding of two unrelated transcription factors to a composite control element