Unit 4: eukaryotic gene control

Eukaryotic cells tend to have gene regulation in ____ potential points

many:

• transcription

• post transcription but before translation

• translation

• post translation

example of eukaryotic gene control during transcription

• transcription factors

• enhancers

• histones

• etc

example of eukaryotic gene control post transcription but before translation

• significant process of turning mRNA into mature mRNA

  • certain areas (introns) of the mRNA are cut out

    • this is a type of regulation bc if they are cut out they will not be expressed (won’t be translated)

Example of eukaryotic gene control during translation

Eukaryotic Initiation Factor 2 (eIF-2) helps translation get started

• eIF-2 can be regulated

• if eIF-2 is phosphorylated (added phosphate group) its shape changes and can no longer initiate transcription

• no protein is made = no gene expression

Example of eukaryotic gene control post translation

• chemical groups can be added or removed from proteins

• this can change where the proteins end up located or how they function

  • therefore impacting their expression

    • eg. environmental factors can influence this (UV, low nutrients, etc)

Ubiquitin

post translation gene control

• regulatory protein

  • ubiquitin tagging = protein degredation (cell death)

what does altering the rate of transcription do?

Its a common method of regulating the expression of eukaryotic genes

Components of eukaryotic genes

• Exons

• Introns

• transcription start site

• promoters

• enhancers

where can the control of gene expression occur

any step in the pathway from gene to functional protein

• packing/unpacking DNA

• transcription

• mRNA processing

• mRNA transport

• translation

• protein processing

• protein degradation

What is DNA packing

DNA packing in gene control refers to how DNA is organized and condensed in the cell, affecting gene expression

Importance of DNA packing

• looser packed DNA = higher transcription

  • transcription factors and RNA polymerase can bind to the gene promoter regions

• Tightly packed DNA = lower transcription

  • prevents the binding of transcription factors and RNA polymerase to the gene promoter regions

negative gene regulation

signaling moleucles interact with repressor proteins that dictate whether a gene will be turned on or off

positive gene control

a signaling molecules generates a complex that interacts with the DNA

how can genes be unaccesible?

the way DNA is wrapped around histones play an important role in gene silencing

• genes bound to histones can’t be expressed

  • to tightly packed

    • rna polymerase can’t access it

how can genes become accessible

Genes become accessible if histones undergo

• acetylation

• methylation

• phosphorylation

This descreases the histones affinity for DNA

• when a gene is no longer coiled around histone it becomes accesible

DNA methylation

• methylation (addition of methyl group) of DNA blocks transcription factors

  • no transcription

  • genes turned off

  • nearly permanent

• attachment of methyl group to cytosine

Histone acetylation

• Acetylation of histones unwinds the DNA

  • enables transcription

    • making it accessible to RNA polymerase and transcription factors

    • genes turned on

  • attachment of acetyl group to histone

    • comfirmaional change in histone proteins (loose)

epigenetics

• the effect of the environment on genes

• epigenetic markers can turn genes on or off (eg. methylation and acetylation)

  • explains why identical twins can be different

• can be inherited from earlier generations

transcription initiation (promoters)

control region on DNA / special region of DNA located near the start of a gene

• It acts like a "signal" or "starting point" that tells the RNA polymerase + transcription factors where to begin transcribing a gene into RNA

• “base rate” of transcription

transcription intitiation (enhancers)

control region on DNA that is located far from the gene (upstream or downstream)

• activator proteins bind to it to increase the rate of transcription

• Enhancers do this by bringing the promoter and transcription machinery closer together, even if they are far apart in the DNA sequence.

purpose of transcription factors

• Transcription factors are proteins that regulate gene expression

• transcription factors help recruit RNA polymerase and other general transcription factors to the gene’s promoter.

• This creates a complex called the transcription initiation complex, which is necessary for the start of transcription.

purpose of transcription initiation complex

• It ensures the accurate and efficient binding of RNA polymerase and transcription factors to the gene, allowing for proper gene expression. Without this complex, transcription cannot begin

How is the transcription initiation complex formed

• Enhancers interact with proteins called activators

• When activators bind to the enhancers, another protein can bend DNA to bring the activators closer to the promoter where the transcription factors can be found

activator proteins

• bind to enhancer sequence and stimulate transcription

• can increase rate of transcription

silencer proteins

bind to enhancer sequence and block gene transcription

Regulation of mRNA degeneration

• life span of mRNA determines amount of protein synthesis

RNA interference

• small interfering RNAs (siRNA)

  • short segments of RNA used to silence genes by binding to and inducing the degradation of specific mRNAs

RNA interference is an example of ——

Post transcriptional control

• turns off genes = no protein produced

how is siRNAs used in research

• siRNAs are widely used in research to silence or knock down specific genes in order to study their function

• siRNA-based therapies are being explored for the treatment of diseases such as cancer, viral infections, and genetic disorders, where the goal is to target and degrade the RNA of disease-causing genes

control of translation

post transcription regulation

• Regulatory proteins attach to the 5’ end of mRNA and blocks initiation of translation stage

  • prevents attachment of ribosomal subunits and initiator tRNA

blocks translation of mRNA to protein

Protein processing

Protein processing refers to the modifications that occur after a protein is synthesized (translated) but before it becomes fully functional.

what does protein processing do

These modifications can activate the protein, enhance its function, or target it to specific cellular compartments.

Types of protein processing

• folding

  • fold to correct 3D structure

• cleaving

  • Many proteins undergo cleavage, where a portion of the protein is cut off. This is often essential for activation

• adding phosphate groups

  • This modification can change the activity, function, or localization of a protein. Phosphorylation is a key regulatory mechanism in cell signaling

• adding sugar groups targeting for transport

  • critical for protein stability, folding, and cell-cell recognition.

Protein degradation

Proteins must be continually degraded and removed to regulate protein levels

protein degredation examples (2)

ubiquitin tagging

• protein is degraded

proteasome degredation

• The proteasome breaks down the protein into small peptides, which are then degraded into amino acids and recycled

summarize gene regulation