Control of Gene Expression in Eukaryotes

Overview of the chapter: Control of gene expression in eukaryotes involves various mechanisms.
Focus on Saccharomyces cerevisiae (yeast) as a model organism.

Key learning outcomes:
- Understanding diverse methods of gene regulation in eukaryotes.
- Exploration of regulation through chromatin, transcription, and comparison with prokaryotes.

Control of Gene Expression

Both prokaryotes and eukaryotes must precisely regulate gene expression to respond to environmental changes.
In multicellular eukaryotes:
- Gene expression affects development and cell type differentiation.
- Differential gene expression leads to variety, with typical human cells expressing about 20% of coding genes.
- Abnormal gene expression can cause developmental anomalies and diseases like cancer.

Eukaryotic gene expression control occurs at multiple levels, including:
- Transcriptional regulation: via histone modifications, DNA methylation, and transcription factors.
- Post-transcriptional regulation: including RNA processing, stability, translation rates, and post-translational modifications.
The variety of regulatory types allows for precise control of gene expression.

Eukaryotic DNA is packaged around proteins (histones) forming chromatin, which allows DNA to fit in the nucleus.
Chromatin structure affects access by transcription factors and RNA polymerase.
Important for gene transcription and DNA replication.

DNA is wrapped around an octamer of histone proteins:
- Group of 8 histone proteins (H2A, H2B, H3, H4).
- This is called a nucleosome.
- Histone H1 causes nucleosomes to form 30-nm fibers crucial for compacting DNA during cell division.

Common post-translational modifications include:
- Acetylation: Addition of acetyl groups by histone acetyl transferases (HATs) increases transcription (opens chromatin).
- Deacetylation: Removal of acetyl groups by histone deacetylases (HDACs) inhibits transcription (closes chromatin).
- Methylation: Can either open or close chromatin depending on location; methyl groups are added by histone methyltransferases.
The Histone Code Hypothesis suggests that combinations of specific histone modifications affect chromatin structure and gene expression.

Epigenetic inheritance refers to phenotype differences inherited independently of DNA sequence changes.
Chromatin modifications can persist across cell divisions:
- Histone patterns are copied to new histones during DNA replication.
- Daughter cells retain information in histone modifications affecting gene expression.
Disruption of these patterns can lead to disease (e.g., cancer).

Famine impacts: Individuals exposed to famine in utero showed different methylation patterns, leading to long-term health effects (e.g., obesity).
- Specific genes (PIM3, PFKFB3, METTL8) involved in metabolic processes exhibited methylation linked to famine exposure.

Involves splicing introns out of primary RNA transcripts leading to different mature mRNAs.
Example: Tropomyosin leads to different proteins in skeletal vs smooth muscle via alternative splicing.

miRNAs regulate gene expression by binding complementary mRNA sequences.
Process of miRNA formation involves:
- Transcription of the miRNA gene.
- Processing by Dicer into mature miRNA.
miRNAs guide RISC to target mRNAs for degradation or translation inhibition.

The rate of translation is variable for different mRNAs.
Regulatory proteins bind mRNA sequences affecting translational efficiency.
Post-translational modifications such as phosphorylation, glycosylation influence protein function and localization.

Regulated by ubiquitin tagging, which marks proteins for destruction by proteasomes.
Ubiquitin-mediated degradation is a critical control mechanism for many cellular processes.

Eukaryotic gene expression can be altered at multiple stages: transcription, post-transcription, translation, and post-translation through complex regulatory networks involving various molecular mechanisms.