The Regulation of Gene Expression

What are the five main levels where eukaryotic gene expression is regulated?

• Genome

• Transcription

• RNA processing and nuclear transport

• Translation

• Posttranslation → posttranscriptional control

Gene amplification

is used to make multiple copies of the same gene

Gene deletion

deletion of a gene

When a gene is being transcribed, its promoter region is embedded within a highly…

folded and ordered chromatin superstructure, this must be unfolded, or decondensed, to allow gene expression

Acetylated, nonmethylated histones favor….

accessibility of chromatin to the transcriptional machinery

Transcriptional control

second main level for controlling gene expression → different cell types transcribe different sets of genes

The specificity of transcription is determined by…

transcription factors (TFs)

General transcription factors are essential for transcription of all genes…

transcribed by a given type of RNA polymerase

Where do general TFs bind?

to core promoter region

where do regulatory TFs bind?

to proximal control elements - transcription activators and repressors

After transcription has taken place, the flow of genetic information inolves…

a complex series of posttranscriptional events

Posttranscriptional regulation is especially useful in…

rapidly fine-tuning patterns of gene expression

RNA splicing regulation allows cells to…

create a variety of different mRNAs from the same mRNA

Alternative splicing permits some….

splice sites to be skipped and other activated

Once mRNAs reach the cytoplasm, several….

translational control mechanisms regulate their rate of translation

Availability of ribosomes or initiation factors…

manipulating elF2 or elF4F phosphorylation

Regulation of mRNA degradation

mRNA stability: long poly(A) tail stabilizes mRNA

Posttranslational control

mechanism modifies protein structure and function

Postranslational control involves….

• reversible structural alterations that affect function

• permanent alteration like proteolytic cleavage

• guiding of proteins to intracellular or extracellular locations

• interactions of proteins with regulatory molecules

Ubiquitin

a small protein containing 76 amino acids

Ubiquitin is joined to target proteins by a process involving…

1. A ubiquitin-activating enzyme (E1)

2. A ubiquitin-conjugating enzyme (E2)

3. A substrate recognition protein, or ubiquitin ligase (E3)

Ubiquitin Targets Proteins for Degradation by Proteasomes: Step 1

ubiquitin is activated by attaching it to E1 in an ATP dependent manner

Ubiquitin Targets Proteins for Degradation by Proteasomes: Step 2

activated ubiquitin is transferred to E2

Ubiquitin Targets Proteins for Degradation by Proteasomes: Step 3

it is linked to a lysine residue in the targeted protein by E3

Ubiquitin Targets Proteins for Degradation by Proteasomes: Step 4

additional ubiquitin is added in sequence

Ubiquitin Targets Proteins for Degradation by Proteasomes: Step 5

this ubiquitin chain serves as a targeting signal for a proteosome, which degrades the protein