2. Learning Objectives

2.5. Eukaryotic Transcription gene regulation

Transcriptional Regulation in Eukaryotes

There are three classes of control elements in eukaryotes:

•The RNA polymerase II binding region (the core promoter)
• cis-acting binding sequences that bind to proteins with RNA polymerase affinity, which in turn help bind RNA polymerase to a promoter.
•A trans-acting DNA element
cis-acting DNA element
•These are short DNA sequences that acts as a binding site for a protein that has an affinity for that specific sequence.
include short consensus sequences
• These elements  are usually located within 200 bp upstream of the transcription initiation site
•They can be included in a promoter or an enhancer
• They have an affinity for a specific protein that binds to it, serving as a regulator
•The term “cis acting” means that the bound protein acts only upon DNA sequences on the same DNA molecule as the cis-acting sequence.
•These are also found in prokaryotes example ; the operator of the lac operon.
cis-acting DNA elements- enhancers and silencers

•An enhancer DNA sequence (or positive regulatory element) turns a gene ON.

•When the activator is bound to the enhancer, RNA polymerase is more highly attracted to the gene.

•enhancers are located upstream or downstream of the promoter region,

•Multiple regulatory proteins bound to binding sites in an enhancer can form a large, complex enhancesosome that has varying affinity for RNA polymerase, depending on its size and exact composition.

•The enhanceosome can both recruit additional co-activators and facilitate chromatin remodeling.

•A silencer DNA sequence (or negative regulatory element) turns a gene OFF or reduces its rate of transcription.

•When the repressor is bound to the silencer, RNA polymerase cannot attach and transcribe the gene.

•silencers are located downstream of a promoter.

Trans-acting DNA element
•A trans-acting DNA element is a DNA sequence that codes for a protein (a trans-acting factor) that controls the expression of a gene at a separate location by binding to its cis-acting element.

 Trans-acting factors:

• These are enzymes that interact with RNA polymerase
• They bind to RNA polymerase to stabilize the initiation complex
• They may bind to a few promoters and serve as positive regulators
•A trans-acting factor can affect the expression of genes located on separate chromosomes.
Post-Translational Control of Gene Expression
  • RNA is transcribed, but must be processed into a mature form before translation can begin. This processing is called post-transcriptional modification. 
  • This post-transcriptional step can also be regulated to control gene expression in the cell. 
  • In eukaryotic  RNA transcript often contains regions, called introns, that are removed prior to translation.
  • The regions of RNA that code for protein are called exons .
  • By a process called , the RNA is processed and the introns are removed and exons are ligated together.

ALTERNATIVE RNA SPLICING
  • Alternative RNA splicing is a mechanism that allows different protein products to be produced from one gene when different combinations of introns, and sometimes exons, are removed from the transcript.
  • Alternative splicing  acts as a mechanism of gene regulation,
  • The frequency of different splicing alternatives controlled by the cell as a way to control the production of different protein products in different cells or at different stages of development.
  •  70 percent of genes in humans are expressed as multiple proteins through alternative splicing.