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 B-DNA

RNAP can back-step!

Transcriptional control (Chapter 7)

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

DNA –> transcription –> RNA –> translation -> Protein

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) -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.

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)

The Lac Operon

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