Lecture 10
Transcription Factor Dimerization and its consequences:
Versatility of the POU proteins
Today we will be discussing the following paper:
Synergy with the coactivator OBF-1 (OCA-B,
BOB-1) is mediated by a specific POU dimer configuration.
Tomilin A, Remenyi A, Lins K, Bak H, Leidel S, Vriend G, Wilmanns M, Scholer
HR.
Center for Animal Transgenesis and Germ Cells Research New Bolton
Center School of Veterinary Medicine Department of Animal Biology University of
Pennsylvania 19348, Kenneth Square, PA, USA
Cell. 2000 Dec 8;103(6):853-64.
The following review article is also very helpful:
Differential activity by DNA-induced
quarternary structures of POU transcription factors.
Remenyi A, Tomilin A, Scholer HR, Wilmanns M.
Biochem Pharmacol. 2002 Sep;64(5-6):979-84. Review.
Important Concepts:
Cooperative DNA-binding:
One of the more important consequences of
protein-protein interaction is the possibility of synergistic
interactions between transcription factors, so that the binding of one
transcription factor makes it easier for the subsequent binding of the other
transcription factors. As a consequence, the amount of transcription
increases in a non-linear way. Cooperative DNA-binding also serves to
effectively increase the specificity of a protein for a specific DNA site.
In addition, it makes binding site occupancy more sensitive to small changes in
protein concentration, making it possible to design a molecular
switch.
Introduction to POU proteins:
Many proteins that regulate gene expression contain a 60 amino acid DNA-binding domain known as the homeodomain. Some of these proteins, for example Oct-1, Oct-2 and Pit-1, have a bipartite DNA-binding region known as the POU domain, which consists of the homeodomain and a POU-specific (Pit, Oct, Unc) domain. The POU-specific domain is composed of 70-75 amino acids and is N-terminal of the homeobox. Such proteins bind to specific DNA sequences and are involved in the temporal and spatial regulation of many genes, some of which are involved in the regulation of neuronal development in the central nervous system of mammals. Additional types of genes regulated by the POU proteins include those for immunoglobulin light and heavy chains (Oct-2), and trophic hormone genes, such as those for prolactin and growth hormone (Pit-1). Both DNA-binding domains of POU proteins are required for high affinity sequence-specific DNA-binding. Crystallographic and biochemical studies have shown that the binary complex provides distinct platforms for the recruitment of specific regulators to control transcription. The paper provides evidence for this.
The Paper
Purpose: Do different POU dimer configurations recruit different coregulatory activities?
MODEL BUILDING
