Gene Expression in Different Cell Types

Gene Expression: Different Cells, Same Genome

• Despite having the same genome, different cell types like neurons and lymphocytes have distinct functions and appearances due to differential gene expression.
• Cells express only a subset of their genes at any given time, allowing specific tasks within an organism.
• Cells can dynamically change the expression of their genes in response to external signals. For example, during starvation or intense exercise, the release of glucocorticoids causes the liver to convert amino acids into glucose. This leads to an increase in the expression of the gene coding for tyrosine aminotransferase, which helps convert tyrosine into glucose.

Variability in Gene Expression

• Many processes are common across all cells, such as the production of structural proteins, DNA and RNA polymerases, and enzymes essential for metabolism.
• Some proteins are highly specialized and abundant in specific cell types, like keratin in surface epithelial cells, hemoglobin in erythrocytes, and muscle fibers in muscle cells.
• Each human cell expresses between 10,000 and 20,000 genes out of the approximate 25,000 genes in the human genome, and the expressed genes vary between cell types.

Prokaryotic Gene Regulation: Operons and Repressors

• The tryptophan operon in bacteria represents a group of genes (open reading frames) controlled by one single promoter, regulating the biosynthesis of tryptophan.
• The tryptophan repressor is a DNA-binding protein that binds to the operator sequence located within the promoter, effectively blocking RNA polymerase from transcribing the operon.
• The repressor binds to the operator only in the presence of tryptophan, acting as a negative regulator of gene expression. When tryptophan is abundant, the repressor binds to the operator, preventing gene expression. When tryptophan is scarce, the repressor detaches from the operator, allowing transcription.

Negative and Positive Regulation

• Negative regulation is mediated by repressors, which modulate gene expression by binding to the operator sequence.
• Repressors can either bind only in the absence of a ligand and disassociate when the ligand binds or bind only in the presence of a ligand and detach when the ligand is removed.
• Positive regulation is mediated by activators, which can stimulate RNA polymerase binding to the operator.
• Activators can either bind to the operator only in the absence of a ligand or only when the ligand is bound to the operator sequence.

Eukaryotic Gene Regulation: More Complex and Dynamic

• Eukaryotic cells use a more complex array of transcription factors compared to bacteria, requiring a more elaborate mechanism for regulating gene expression.
• To overcome promoter crowding, eukaryotic gene regulatory proteins can act thousands of nucleotides away from the transcriptional start site.
• DNA bending and looping facilitate the interaction of regulatory proteins with the transcriptional machinery, allowing for a large number of regulatory elements to control a single gene.

Enhancers and Activators

• Activators can bind to enhancer sequences, which are located upstream of the promoter, and facilitate gene expression by promoting RNA polymerase recruitment through DNA bending.
• Eukaryotic gene regulatory proteins recognize and bind to specific DNA binding sites, enabling gene expression by recruiting RNA polymerase and other transcription factors.

Chromatin Remodeling

• Chromatin remodeling is essential for the accessibility of DNA to the transcriptional machinery.
• This can be achieved through two main mechanisms:
  • Chromatin remodeling complexes, which alter nucleosome positioning.
  • Histone acetylation by histone acetyltransferases (HATs), which loosens chromatin structure.

Repression of Gene Expression in Eukaryotes

• There are five known mechanisms for eukaryotic gene repression:
  • Repressors bind to DNA binding sites, preventing activator binding.
  • Repressors bind to the activation domain of nearby activators, inhibiting their activity.
  • Repressors interact with transcription factors, preventing the binding of the holoenzyme to the promoter.
  • Repressors recruit chromatin remodeling complexes, which condense chromatin and hide the promoter sequence.
  • Repressors attract histone deacetylases, which remove acetyl groups from histones, promoting tighter chromatin structure and preventing TFIID binding.

Activating Gene Regulatory Proteins

• Gene regulatory proteins can be activated through various mechanisms:
  • Some proteins are only synthesized when needed and rapidly degraded inside the cell.
  • Others require binding to a specific ligand to become active.
  • Certain proteins must be phosphorylated to become active.