Chapter 14- Gene regulation eukaryotic expression

Describe the flow of genetic information and recognize that sometimes it ends with RNA molecules that have specialized jobs (not every RNA is translated into a polypeptide).

The flow of genetic information follows this sequence:

1. DNA → RNA → Protein

   • DNA is transcribed into RNA.

   • RNA is translated into a protein.

However, not all RNA molecules are translated into proteins—some have specialized functions.

Steps in the Flow of Genetic Information

1. Transcription (DNA → RNA)
   
   

   • Occurs in the nucleus (eukaryotes) or cytoplasm (prokaryotes).

   • RNA polymerase reads the DNA template and synthesizes messenger RNA (mRNA).

   • The mRNA is processed (capping, splicing, polyadenylation) before export to the cytoplasm.

2. Translation (RNA → Protein) [For mRNA]
   
   

   • Occurs in the cytoplasm.

   • Ribosomes read the mRNA sequence and assemble amino acids into a polypeptide.

Specialized RNA Molecules (Not Translated into Proteins)

Some RNA molecules perform functional roles without being translated into proteins:

1. Transfer RNA (tRNA) – Carries amino acids to ribosomes during translation.

2. Ribosomal RNA (rRNA) – A structural and enzymatic component of ribosomes.

3. MicroRNA (miRNA) – Regulates gene expression by degrading or blocking mRNA translation.

4. Small Interfering RNA (siRNA) – Involved in RNA interference (RNAi) to silence genes.

5. Long Non-Coding RNA (lncRNA) – Regulates gene expression and chromatin structure.

6. Small Nuclear RNA (snRNA) – Plays a role in mRNA splicing.

Thus, while mRNA leads to proteins, many RNA molecules have independent cellular functions essential for gene regulation and expression.

Be able to define differentiation (cell fate) and understand what it means that all of your somatic cells are genetically equivalent.

Differentiation (Cell Fate): The process by which a less specialized cell becomes a more specialized cell type, such as a muscle cell, neuron, or skin cell.

Genetic Equivalence: All somatic (non-reproductive) cells in an organism have the same DNA. However, different cell types express different genes due to regulation at multiple levels.

Know and explain the different levels of gene expression control and what molecule they specifically regulate (DNA, RNA or protein).

Gene expression is regulated at multiple levels, affecting different molecules:

1. Chromatin structure (Epigenetic Regulation) → DNA

   • Histone modifications (acetylation, methylation)

   • DNA methylation

2. Transcriptional Control → DNA to RNA

   • Transcription factors binding to control elements

   • Enhancers, silencers, and the Mediator complex

3. Post-transcriptional Control → RNA

   • Alternative splicing

   • mRNA stability and degradation

   • microRNAs (miRNAs)

4. Translational Control → RNA to Protein

   • Ribosome availability

   • Translation initiation factors

5. Post-translational Control → Protein

   • Protein modifications (phosphorylation, ubiquitination)

   • Protein degradation and trafficking

Define epigenetics. Understand how different histone tail modifications can loosen or condense chromatin, can activate or repress gene expression. Know how DNA methylation can change gene expression - reversible DNA modifications that activate or repress gene expression and can be inherited.

Definition: Heritable changes in gene expression that do not alter the DNA sequence.

Histone Modifications:

• Acetylation (HATs, Histone Acetyltransferases): Loosens chromatin → Gene activation

• Deacetylation (HDACs, Histone Deacetylases): Condenses chromatin → Gene repression

• Methylation: Can either activate or repress gene expression depending on the histone and the specific modification.

DNA Methylation:

• Methyl groups (-CH3) are added to cytosine bases in CpG islands → Gene silencing

• Reversible and can be inherited through cell divisions

Describe the function of transcription factors - general and specific transcription factors.

General TFs: Required for the transcription of all genes; help position RNA polymerase at the promoter.

Specific TFs: Bind to enhancers or silencers to increase or decrease transcription.

Function: Recognize specific DNA sequences (promoters, enhancers) and recruit co-activators or repressors.

What do they recognize in DNA, which proteins do they interact with, what protein are they required to recruit?

Proteins, specifically transcription factors, recognize specific DNA sequences (promoter regions) and interact with other proteins, including RNA polymerase and chromatin-modifying enzymes, to regulate gene expression and recruit the necessary machinery for transcription. 

Know what the control elements around a gene are and what proteins bind to them.

Proximal control elements: Close to the promoter, bind transcription factors to regulate transcription.

[Activators (proteins like transcription factors that bind enhancer DNA elements to increase expression) and repressors (proteins that bind silencer DNA sequences to decrease expression) can bind to control elements to influence gene expression.]

What DNA sequence binding sites for transcription factors assist with gene expression; proximal elements – close to promoter; enhancer elements – can be near or far, many or few.

• Proximal control elements: Close to the promoter, bind transcription factors to regulate transcription.

• Enhancer elements: Can be far away, increase gene expression by binding activators.

• Silencer elements: Bind repressors, reducing transcription.

Know what the Mediator complex’s job in transcription initiation is.

• A large protein complex that bridges transcription factors and RNA polymerase II.

• Helps integrate signals from activators and repressors to control gene expression.

Be able to describe how RNA molecules can be modi*ied, stabilized, translated and/or targeted for degradation.

RNA Modifications:

• 5’ cap & poly-A tail (stabilization, nuclear export)

• Alternative splicing (creates different protein isoforms)

RNA Stability & Degradation:

• microRNAs (miRNAs) and small interfering RNAs (siRNAs) can target mRNA for degradation.

Understand the two examples of post-translational (“after the protein is made”) regulation– modification and trafficking vs. removal.

Modification:

• Phosphorylation, methylation, ubiquitination alter protein function.

Trafficking vs. Removal:

• Proteins can be tagged with ubiquitin for degradation in the proteasome.