Gene Regulation and Expression

Gene Regulation and Expression

• Concerns the control of which genes are turned on or off, dictating the flow of information from genotype to phenotype
• This regulation leads to cell specialization in structure and function.
• Regulatory dimensions include time, space, and abundance of gene products

Gene Expression

• Altered in response to changing environments in both prokaryotes and eukaryotes
• Regulated to direct development and account for cell type differences in multicellular eukaryotes
• RNA molecules play significant roles in gene regulation in eukaryotes

Categories of Genes

• Housekeeping genes are always active in all cells for basic functions like transcription and energy conversion
• Cell type-specific genes dictate special properties and functions in particular cell types
• Developmental regulatory genes are activated during specific growth and development stages
• Inducible genes are typically not expressed but can be activated in response to hormones or other external stimuli

Operons

• Operons are the entire DNA stretch including the operator, promoter, and genes they control.
• The operator is a regulatory switch within a DNA segment.
• It is positioned between enzyme genes and the promoter
• The promoter contains a site where transcription enzymes initiate transcription upon RNA polymerase and transcription factor (TF) binding
• Repressors prevent transcription by binding to the operator, blocking RNA polymerase and are products of separate regulatory genes, functioning in either active or inactive forms
• Inducers activate or inactivate repressors
• Activators accelerate transcription
• Enhancers are distal control elements in operons

Bacteria Response to Environmental Change

• Natural selection favors bacteria that produce only necessary products
• Cells regulate enzyme production through feedback inhibition
• Gene regulation occurs on a DNA stretch to coordinate gene expression
• Bacterial gene expression is controlled by the operon model

trp Operon

• If tryptophan is present, it binds to the trp repressor, turning the operon off
• The trp operon is on and transcribes synthesis genes when tryptophan is absent
• The repressor activates when a corepressor is present; the trp operon is then repressed if tryptophan levels are high

lac Operon

• The lac operon is for lactose enzymes used in hydrolysis and metabolism
• By itself, the lac repressor is active and switches the lac operon off
• The inducer inactivates the repressor to turn the lac operon on

Negative Gene Regulation

• Repressible operons are typically on, shut off when a repressor binds the operator, exemplified by the trp operon
• Inducible operons are typically off, activated by an inducer inactivating the repressor, like the lac operon
• Repressible enzymes function in anabolic pathways, their synthesis repressed by high product levels
• Inducible enzymes function in catabolic pathways, their synthesis induced by a chemical signal

Positive Gene Regulation

• This process uses stimulatory proteins like Catabolite Activator Protein (CAP)
• When glucose is scarce, CAP is activated by cAMP
• Activated CAP increases affinity of RNA polymerase to the lac operon promoter, accelerating transcription
• When glucose levels rise, CAP detaches, and transcription returns to normal rate
• CAP helps regulate other operons for catabolic pathways

Eukaryotic Gene Expression

• It must be regulated at given times and stages, essential for cell specialization
• Differential gene expression causes cell type differences
• It causes cells with the same genome to express different genes
• Abnormalities in expression could lead to diseases

Regulation of Chromatin Structure

• Chromatin structure and gene expression are influenced by modification to histones and DNA
• Highly packed heterochromatin is not typically expressed
• Loose euchromatin facilitates gene expression
• Histone acetylation (addition of acetyl groups) loosens chromatin, promoting transcription
• Methylation (addition of methyl groups) condenses chromatin
• Phosphorylation (addition of phosphate groups) loosens chromatin when next to a methylated amino acid

Histone Code Hypotheses

• Specific modification combinations and their order determine chromatin configuration and influence transcription

DNA Methylation

• This involves the addition of methyl groups to certain DNA bases
• It is associated with reduced transcription in some species
• It causes long-term gene inactivation in cellular differentiation
• In genomic imprinting, it regulates maternal or paternal allele expression at the start of development

Epigenetic Inheritance

• Chromatin modifications that do not alter DNA sequences can be passed to future generations
• The inheritance of traits via mechanisms not directly involving nucleotide sequences constitutes epigenetic inheritance

Eukaryotic Gene Organization

• Multiple control elements are binding sites for Transcription Factors (TFs) that help regulate transcription
• Control elements and TF binding ensure precise gene regulation in different cell types

Transcription Factors (TFs)

• These are proteins that are essential to RNA polymerase initiation of transcription
• General TFs transcribe all protein-coding genes
• High/low levels of transcription are dependent on control elements interacting with specific TFs
• TFs control various processes like development, cell cycle, and responses to environment

Transcription Initiation Regulation

• Transcriptional regulation in eukaryotes is complex.
• Transcription Factors (TFs) along with enhancers regulate this process
• Sequences to which TFs bind are called TFBSs (cis-regulatory elements)
• Repressors inhibit transcription by binding to DNA sequences called silencers
• Chromatin-modifying enzymes control gene expression by affecting DNA's ability to bind the transcription machinery

Enhancers and Transcription Factors

• Proximal elements are located near the promoter
• Distal elements (enhancers) can be far from the gene or in an intron
• An activator binds to an enhancer stimulating gene transcription
• Activators have two domains; one binds DNA, the other activates transcription
• Bound activators facilitate transcription through protein-protein interactions

Eukaryotic Genes

• All genes co-expressed eukaryotes each have a promoter and control elements
• They can be scattered over different chromosomes but share control element combinations
• Activator copies recognize these elements to promote simultaneous transcription

Post-Transcriptional Regulation

• Regulatory mechanisms operate at various stages to allow fine-tuning gene expression rapidly via environmental changes
• Alternative RNA splicing produces different mRNA molecules from the same transcript.
• mRNA has processes include the addition of a cap, removal of introns, and splicing together remaining exons

mRNA Degradation

• mRNA lifespan in the cytoplasm determines protein synthesis
• Molecules are eventually broken down and recycled
• Eukaryotic mRNA has a longer lifespan compared to prokaryotic mRNA
• Nucleotide sequences at the 3' untranslated region (UTR) influence the mRNA lifespan

Translation Initiation

• The initiation of translation of selected mRNAs can be blocked by regulatory proteins that bind to sequences or structures of the mRNA.
• Alternatively, translation of all mRNAs in a cell may be regulated simultaneously.
• Post-Translational Control Mechanisms happens after translation by involving, for example, cutting polypeptides into smaller active products

Protein Processing and Degradation

• Post-translational protein processing can be subject to control
• Proteasomes degrade protein molecules that are bound to them