Control of Gene Expression in Eukaryotes

Control of Gene Expression in Eukaryotes

Overview

• Gene expression in eukaryotes is more complex than in prokaryotes.
• Regulation of gene expression is essential for maintaining cell functionality.
• Regulatory proteins, in addition to transcriptional enzymes, control gene expression levels.

Transcription Factors

• Transcription factors are proteins that activate transcription by searching DNA for specific binding motifs.
• They have two domains:
  • DNA binding domain: binds to specific nucleotide sequences in the promoter region or DNA response elements.
  • Activation domain: binds other transcription factors, regulatory proteins (e.g., RNA polymerase, histone acetylases).
• DNA response element: A sequence of DNA that binds only to specific transcription factors to help in the recruitment of transcriptional machinery.

Gene Amplification

• Basal transcription maintains adequate protein levels.
• Expression can be increased or amplified via enhancers and gene duplication.

Enhancers

• Response elements outside promoter regions are recognized by transcription factors to enhance transcription.
• Enhancers: Grouped response elements that allow multiple signals to control a gene's expression.
• Signal molecules (e.g., cyclic AMP (cAMP), cortisol, estrogen) bind to specific receptors.
  • Examples:
    • cAMP binds to cyclic AMP response element binding protein (CREB).
    • Cortisol binds to the glucocorticoid receptor.
    • Estrogen binds to the estrogen receptor.
  • These receptors act as transcription factors binding to response elements within the enhancer.
• DNA often bends into a hairpin loop to bring enhancers and promoters together due to the large distance between them.
• Enhancers can be up to a thousand base pairs away from the gene and can be located within introns.
• Upstream promoter elements must be within 25 bases of the start of a gene.

Gene Duplication

• Cells increase gene product expression by duplicating the gene.
• Duplication can occur:
  • In series: multiple copies in a row on the same chromosome.
  • In parallel: opening the gene and replicating it multiple times, resulting in hundreds of copies on the same chromosome.

Regulation of Chromatin Structure

• DNA is packaged as chromatin in eukaryotic cells.
• Chromatin remodeling is required for transcription factors and machinery to access DNA.

Heterochromatin

• Tightly coiled DNA; appears dark under a microscope.
• Inaccessible to transcription machinery; genes are inactive.

Euchromatin

• Looser DNA; appears light under a microscope.
• Accessible to transcription machinery; genes are active.

Histone Acetylation

• Transcription factors recruit co-activators like histone acetylases.
• Histone acetylases acetylate lysine residues on histone proteins.
• Acetylation reduces the positive charge, weakening histone-DNA interaction.
• This results in an open chromatin conformation.
• Increased gene expression levels can result from specific histone acetylation patterns.

Histone Deacetylation

• Histone deacetylases remove acetyl groups from histones.
• This results in a closed chromatin conformation and decreased gene expression.

DNA Methylation

• DNA methylases add methyl groups to cytosine and adenine nucleotides.
• Methylation is associated with gene silencing.
• Plays a role in silencing genes during development.
• Heterochromatin regions are heavily methylated.

Conclusion

• The human body produces approximately 100,000 different proteins from 20,000-25,000 genes.
• Proteins are produced through the central dogma: DNA transcribed into mRNA, then translated into protein.
• Transcription, translation, and their regulation occur in both prokaryotes and eukaryotes.
• Organelles such as the nucleus, nucleolus, ribosome, rough endoplasmic reticulum, and Golgi apparatus play important roles.
• Secreted proteins (e.g., hormones, digestive enzymes) are transported to the plasma membrane for exocytosis.