In-Depth Notes on Gene Expression & Regulation

Gene Expression and Regulation

• Gene Expression: The process through which genetic information is used to synthesize gene products (usually proteins). This includes transcription and translation steps, alongside regulation mechanisms that control when and how genes are expressed.

• Somatic Cells:

  • Diploid: Contain two sets of chromosomes, one from each parent.
  • Same DNA: All somatic cells share the same genetic material, but express different genes to fulfill various functions (e.g., muscle vs. nerve cells).
  • Cell Differentiation: During development, cells specialize in function and form due to regulated gene expression.

• Gene Regulation:

  • Essential for managing cellular activities, optimizing resource use (energy, space, time), particularly during development and differentiation.
  • Regulation impacts which genes are expressed, influencing cell type and function.

Prokaryotic Gene Regulation

• Operons:

  • Groups of genes with a shared regulatory mechanism, organized in the prokaryotic circular DNA. Common types include:
  • Repressible Operons: Regulated by repressors, which inhibit gene expression based on internal cellular conditions.
  • Inducible Operons: Can be activated (or repressed) by inducers in response to environmental signals (e.g., lac operon).

• Types of Regulatory Molecules in Prokaryotes:

  • Repressors: Decrease gene expression by blocking transcription.
  • Activators: Enhance gene expression by facilitating transcription.
  • Inducers: Compounds that either activate or inhibit transcription based on cellular needs.

• Example - Lac Operon:

  • Utilized to metabolize lactose when glucose levels are low.
  • Mechanism:
  • If lactose is absent, the LacI repressor binds to the operator, inhibiting RNA polymerase and halting transcription.
  • When lactose is present, it binds to the repressor, allowing RNA polymerase to transcribe the genes downstream (lacZ, lacY, lacA).

Eukaryotic Gene Regulation

• Transcription Factors (TFs):

  • Proteins that bind to specific DNA sequences (promoters and enhancers) to control transcription.
  • Can act as activators or repressors, influencing when and how much gene product is made.

• Epigenetic Modifications:

  • Changes in gene expression without altering DNA sequence.
  • Examples:
  • Chromatin Structure: Chemical modifications (e.g., histone acetylation) modify accessibility of DNA.
  • Transcriptional Regulation: Involves enhancers and repressors that modulate transcription initiation.
  • Post-Transcriptional Regulation: Involves mRNA processing and stability (e.g., splicing, capping).

• RNA Processing: Required before mRNA can be translated in the cytoplasm. Key steps include the addition of the 5’ cap, poly-A tail, and alternative splicing.

Translation Regulation in Eukaryotes

• Initiation: Regulated by initiation factors that help assemble the ribosome and initiate translation. This includes eukaryotic initiation factor-2 (eIF-2).

• Post-Translational Modifications:

  • Changes that affect protein activity, such as phosphorylation and ubiquitination that can tag proteins for degradation.

Cancer and Cell Cycle Regulation

• Checkpoints: Ensure proper progression through the cell cycle (G1, G2, M).

  • Positive Regulators: Promote cell cycle advancement (e.g., cyclins, proto-oncogenes).
  • Negative Regulators: Prevent progression and monitor for issues (e.g., tumor suppressor genes like p53).

• Cancer Development:

  • Arises from genetic mutations affecting normal controls over cell growth and division.
  • Factors include environmental triggers (carcinogens), inherited mutations (e.g., BRCA genes), and dysfunction of regulatory pathways.

• Mechanisms of Tumor Spread: Cancer cells may invade local tissue and metastasize to distant parts of the body through blood and lymphatic systems, forming new tumors.

Summary of Eukaryotic vs. Prokaryotic Gene Expression

• Prokaryotic Cells:

  • Circular DNA, simultaneous transcription and translation, primarily regulation at the transcriptional level.

• Eukaryotic Cells:

  • Linear DNA within nucleus, separate transcription and translation processes, multiple levels of gene expression regulation (epigenetic, transcriptional, post-transcriptional, translational, and post-translational).