Chapter18-Gene Regulation

Gene regulation refers to the control of when and how much of a gene is expressed.
Both prokaryotes and eukaryotes can alter gene expression in response to changing environmental conditions.
- Example: E. coli adjusts its gene expression based on the variable diet of its host.
- This ability allows E. coli to change metabolic pathways for the synthesis of essential nutrients and enzymes not supplied by the host's diet.

Bacteria respond to environmental changes primarily by regulating transcription.
- Natural selection favors bacteria that produce only the necessary cellular products.
Regulation of enzyme production can occur through:
- Feedback Inhibition
- A process where the end product of a metabolic pathway inhibits an earlier step in the pathway.
- Gene Regulation
- Through the operon model, which demonstrates how gene expression can be turned on and off.

Operon: A DNA sequence that incorporates structural genes and regulatory elements that control transcription.
- Key Elements of an Operon:
- Promoter: The specific DNA sequence where RNA polymerase attaches to initiate transcription.
- Structural Genes: Any gene that encodes a polypeptide.
- Repressor: A regulatory protein that binds to DNA, preventing RNA polymerase from initiating transcription.
- Corepressor: A small molecule that works with the repressor to turn the operon off.
- Operator: A DNA sequence that acts as a binding site for the repressor.
- Transcription Terminator: A DNA sequence that signifies the end of transcription.

Transcription is typically active but can be inhibited when a small molecule binds allosterically to a regulatory protein.
Example: Tryptophan operon (trp operon)
- The repressor remains inactive when tryptophan is absent, allowing for transcription.
- When tryptophan is available, it binds to the trp repressor, activating it, and the repressor then binds to the operator, stopping transcription.

Generally inactive but can be activated when a small molecule interacts with the regulatory protein.
Example: Lactose operon (lac operon)
- In the absence of lactose, the repressor binds the operator, preventing transcription.
- When lactose is present, it binds to the repressor, inactivating it and allowing transcription.

Key Components:
- Structural genes: lacZ, lacY, lacA
- lacZ - encodes beta-galactosidase, which breaks down lactose into glucose and galactose.
- lacY - encodes permease, which facilitates lactose entry into cells.
- lacA - encodes transacetylase, function still not well-defined.
The repressor protein, under certain conditions, can inhibit RNA polymerase from transcribing the operon.

Negative Regulation: Operons like lac and trp are negatively regulated since transcription is turned off by the active repressor.
Positive Regulation: A regulatory protein interacts directly with the genome to induce or turn on transcription.

Unlike prokaryotes, eukaryotic cells typically express about 20% of their genes at any given time; all cells share an identical genome but differ in gene expression profiles.
About 1.5% of human DNA encodes functional proteins, with the remainder being non-coding RNA or non-transcribed.
Regulation occurs mainly during:
- Transcription
- Also significant control points include:
- Translation
- Protein Processing and Degradation
- Regulation of Chromatin Structure
- mRNA Degradation
- RNA Processing

Chromatin Modification
- Nucleosomes: Basic units of DNA packing in eukaryotes, giving structure to chromatin via a 'bead on a string' model.
- Genes in compact chromatin are generally not transcribed.
- Histone Acetylation: Loosens chromatin structure, promoting transcription.
- DNA Methylation: Reduces transcription; can be linked to long-term gene silencing.

Histones can be modified by:
- Acetyl Groups: Enhance transcription by relaxing chromatin.
- Methyl Groups: Can decrease transcription.
- Phosphate Groups: Generally associated with reduced transcription.
Histone Code Hypothesis: The belief that specific histone modifications can be interpreted to control gene expression.

Mechanism by which traits are passed to offspring without altering DNA sequence.
Methylation: Involves in long-term gene inactivation, with patterns that can be inherited.
Example: Studies reveal how nutrition affects epigenome, with implications for health based on parental diets.

Study example: Mice with unmethylated agouti gene leading to obesity and diabetes; dietary methylation led to healthier offspring with brown coats and normal weight.

Chemical alterations can expand or compact chromatin, thus affecting gene activity.
Eukaryotic transcription complexity includes numerous control elements and enhancers leading to precise regulation.

RNA polymerase requires assistance from various proteins (transcription factors) for initiation.
Activators: Bind to enhancers to stimulate transcription through DNA bending, enabling contact with other proteins at the promoter.

Alternative RNA Splicing: Produces different mRNA molecules from the same primary transcript by altering which segments are treated as exons.
mRNA Lifespan: Influenced by untranslated regions (UTRs) and begins with shortening of the poly-A tail leading to removal of the 5' cap.

Regulation at various stages (transcription, processing, translation, post-translation) allows for adaptable protein synthesis based on cellular needs and environmental cues.
Global control can simultaneously regulate all mRNAs within a cell, influenced by specific factors necessary for translation initiation.

Following translation, proteins undergo modifications which can affect function and stability.
- Ubiquitin tagging signals proteins for degradation via proteasomes.