Chromosome Organization

Overview

• Discussion on chromosome organization, emphasizing dynamic nature
• Chromosomes appear different in various cell cycle stages

Chromosome Appearance in Cell Cycle

• Interphase: Beads on a string appearance
• Prophase: Densely packed chromosomes
• Metaphase: Characteristic egg-shaped structure
• Chromosomes are dynamic, changing appearance similar to human age changes

Nucleosomes

• Basic unit of chromosome composed of DNA and histone proteins
• Histones: Basic proteins with lysine and arginine
  • Canonical histones: H3, H4, H2A, H2B
  • Form dimers, then tetramers, culminating in histone octamer
• Structure: Approximately 200 base pairs of DNA wrap around histone octamer (1.6 left-handed superhelical turns)

Higher Order Chromatin Structure

30 Nanometer Fiber

• More organized than the beads on a string
• H1 Histones: Assist in formation of this structure
• Models:
  • Solenoid model: Consecutive nucleosome interactions
  • Zigzag model: Alternate nucleosome interactions
• Current understanding based on in vitro data with ongoing debates about models

300 Nanometer Fiber

• Assembly of beads on a string into a more complex structure

Factors Determining Chromatin Condensation

• Cohesins and Condensins: Key proteins aiding in chromosome structure, compaction, and separation during anaphase
• Cohesin breakdown allows chromatids to be pulled apart

Electron Microscopy Studies

• Identified two chromatin types:
  • Heterochromatin: Densely stained and transcriptionally inactive
  • Euchromatin: Lightly stained, transcriptionally active

Chromatin Modifications

• Euchromatin

  • Loosely packed, highly acetylated (e.g., H3K9, H3K27 acetylation)
  • Activatory methylations (e.g., H3K4Me2, H3K36Me3)
  • Phosphorylation (e.g., H3S10)

• Heterochromatin

  • Densely packed, less acetylated
  • Specific methylation patterns aiding in compaction
  • Histone variants associated with heterochromatin (H3.1, H3.2, etc.)

Chromatin Accessibility

• Accessibility essential for transcription
• Transcription factors and machinery need access to chromatin
• Nucleosome Remodeling Factors: Key players in chromatin accessibility
  • Use ATP to remodel chromatin
  • Histone eviction, replacement, and sliding can enhance accessibility

ATAC Sequencing

• High-throughput technology used to study chromatin accessibility

3D Organization of Chromatin

• Chromosomes exist in a 3D volume, not 2D
• Chromosome Territories: Specific regions for each chromosome
• Topologically Associated Domains (TADs): Regions that interact in 3D space
  • Can involve intra- and interchromosomal interactions
• Enhancer-promoter loops facilitate transcription regulation

Hi-C Technique

• Captures 3D chromatin conformation and interactions
• Provides correlation maps to study chromatin dynamics and interactions

Conclusion

• Summary of chromosome organization and factors affecting it
• Discussion on histone modifications, DNA modifications, and their roles in chromatin states
• Importance of 3D organization in gene regulation and chromatin dynamics

Additional Resources

• Links to further readings and videos available in descriptions.