Regulation of Gene Expression in Eukaryotes

Regulation of Gene Expression in Eukaryotes

• Eukaryotic cells control gene expression at multiple levels
• Humans have ~200 major cell types, yet share the same genome
• Different cell types express different sets of genes

Eukaryotic Gene Regulation

• Cells control gene expression through epigenetic, transcriptional, and translational control

Chromatin Remodeling

• DNA in chromatin is inaccessible to the transcription machinery until remodeled
• Tightly coiled chromatin limits access to promoters/enhancers
• Chemical modifications of histone tails reposition nucleosomes and expose DNA to the transcription machinery.
• This occurs during development and in response to environmental cues

Histone Tail Modifications

• Histone code affects chromatin structure and gene transcription.
• The modifications include methylation (mono, tri, etc), acetylation

DNA Methylation

• Light methylation of CpG islands allows transcription.
• Heavy methylation of CpG islands inhibits transcription.
• DNA methylation can recruit proteins to remodel chromatin and modify histone tails

Epigenetic Effects

• Epigenetic effects are changes in gene expression without changing DNA sequence
• These changes can be inherited but often are reversible and responsive to environmental changes

Epigenetic Adaptations

• Environmental toxins, stress, smoking, diet, and aging can influence epigenetic adaptations, impacting subsequent generations
• Epigenetic disorders and epigenetic-based therapies can be used

Repressed vs. Active Chromatin

• Repressed chromatin is heavily methylated and is associated with deacetylated and methylated histones
• Active chromatin is lightly methylated and associated with acetylated and deacetylated histones
• Histone acetylation and methylation can change the structure of DNA, enabling or preventing transcription

X-inactivation

• X-inactivation occurs in the early embryo, often around the time of implantation
• In each cell linage, the inactivated X chromosome remains inactivated
• The Xist gene is transcribed, and the Xist RNA binds to the X-chromosome in the inactivation center, effectively inactivating the X-chromosome

Transcriptional Control

• General transcription factors bind the promoter
• Transcriptional activator proteins bind to enhancers
• DNA looping brings these factors together, allowing transcription

Regulatory Transcription Factors

• Regulatory transcription factors bind to DNA sequences
• These sequences are called enhancers or silencers
• Activators or repressors can bind to these sequences to turn on or off gene expression, influencing transcription
• These sequences can be located far from promoters but still affect transcription

Translational Regulation: Small Regulatory RNAs

• Precursors of small regulatory RNAs (e.g., siRNAs, miRNAs) are processed in the cytoplasm
• These fragments target complementary mRNA sequences through translational inhibition
• siRNAs pair perfectly with a target mRNA resulting in degradation of the mRNA
• miRNAs have mismatches leading to translational inhibition

Translational Regulation: Proteins that Bind UTRs

• Proteins can bind to sequences in the 5' and 3' untranslated regions (UTRs) of mRNA
• These proteins influence the location and regulation of translation initiation.
• This impact mRNA stability

Post-transcriptional Regulation of Gene Expression

• Iron-response element activity is regulated to ensure appropriate iron levels for cell function
• These factors regulate various cellular processes, including gene expression, translation and mRNA stability.
• The most common mechanism of translational regulation is initiation.
• Binding proteins can block ribosomes.

Gene Regulation- Iron Metabolism

• Humans require iron for red blood cell production (-20 mg/day).
• Excessive iron is toxic
• Iron transport proteins (transferrin, transferrin receptors) and storage protein (ferritin) are critical

Elements of Iron Response

• mRNA for ferritin and transferrin receptor have iron response elements (IRE)
• Binding proteins (IRE-BPs) modulate mRNA stability and translation based on iron levels.
• Iron-dependent conformation changes of IRE-BP control when the mRNA is translated

Explore how eukaryotic cells regulate gene expression at various levels, including epigenetic, transcriptional, and translational controls. This quiz covers key concepts such as chromatin remodeling and histone tail modifications that impact gene transcription.