Biochemistry Online: An Approach Based on Chemical Logic

Biochemistry Online




Last Updated: 03/30/16

Learning Goals/Objectives for Chapter 5D:  After class and this reading, students will be able to

  • describe general mechanisms of how a gene for a given protein might be negatively and positively regulated at the level of gene transcription;
  • describe the structure/function/role of promoters, response elements, RNA polymerase, transcription factors, nucleosomes, histone proteins, epigenetic modifications of DNA in gene transcription;
  • explain the differences (structural, Kds) between specific and nonspecific binding of a ligand to a macromolecule, at the structural level;
  • describe the structural features of both proteins and DNA that result in specific and nonspecific binding;
  • describe and give examples of how post-translational modifications of proteins and epigenetic modifications of DNA can alter gene expression;
  • explain how the apparent Kd for a protein binding to DNA can be altered by the presence of another protein bound to DNA at a proximal site
  • describe the basis of RNA interference in gene expression

D3.  Control of Gene Transcription in Eukaryotes


Three major differences exists in the control mechanisms used to regulate gene transcription in eukaryotes compared to prokaryotes.

The genomes of eukaryotes are much larger than prokaryotes. This poses some problems with respect to binding. Remember, DNA binding proteins demonstrate both nonspecific and specific binding. Nonspecific binding may help a protein find a specific site in the genome, but as the size of the genome increases, the chance of finding multiple specific sites randomly distributed increases. This problem can be avoided if multiple proteins are required to generate an active transcription complex. The chance of finding two or more specific sites for different proteins in proximity at sites other than required for gene transcription are very low. Multiple negative regulators would not be needed since just the binding of one regulator would probably be sufficient. Most eukaryotic genes have about 5 regulatory sites for binding transcription factors and RNA polymerase. Examples of these transcription factors are show in the figure below.

Figure:  Control of globin gene transcription

Figure:  Example of transcription complexes

(reprinted with permission from Kanehisa Laboratories and the KEGG project: )

Light can even regulate gene expression by indirectly activating an inactive transcription factor in plants.  The  transcription factor PIF3 binds to a promoter region (G-box) of light-responsive genes. Only when PIF3 binds another transcription factor, Pr, is transcription activated.  Pr, a "photoreceptor" is found in an inactive form in the cytoplasm.  When it absorbs red light, it undergoes a conformational shift and moves into the nucleus, where it can bind PIF3 and activate transcription.  The activation complex is inactivated when Pr interacts with far-red light.

Figure:  Upon absorbing red light, a phytochrome photoreceptor is converted from the inactive Pr form to the active Pfr form

p53 information from the HHMI

animation: p53 and gene transcription from the HHMI (loads slowly)


Return to Chapter 5D: Binding and the Control of Gene Transcription

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 Archived version of full Chapter 5D:  Binding and the Control of Gene Transcription


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