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Lecture 12
RNA polymerase as a molecular motor
Transcriptional control
RNA polymerase as a molecular motor
from Gelles 1998
From S. Block
Average step size =
3.7A, which
corresponds to the
base spacing in BDNA
RNAP can back-step!
Transcriptional control (Chapter 7)
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 (CAPcAMP) 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.
Leucine Zipper and basic Helix-Loop-Helix proteins
Ligand binding changes conformation of the estrogen receptor
Cooperative binding of two unrelated transcription factors
to a composite control element