Introduction
Chromosome and DNA Condensation
- DNA Condensation in Chromosomes
- Interphase: 1000-fold compaction
- Metaphase: 10,000-fold compaction
- Nucleosomes: 147bp of DNA around a histone octamer; the functional unit.
Chromosome Structure
- Parts of a Chromosome
- Arms, Centromere, Telomere (ends)
- Hierarchical Structure
- Nucleosome, Domain, Chromosome level
Chromosome Folding
- Increments
- Folded into compartments (A: open/active, B: closed/silent)
- Chromatin in TADs, then sub-TADs.
- Chromosome Territory: Specific nuclear region per chromosome.
TADs and Chromatin Compartments
- TAD: Self-interacting region, maintained by architectural proteins.
- A vs. B Compartments
- A: Active, gene-rich, nucleus interior.
- B: Inactive, gene-poor, compact, nucleus periphery, mainly LAD.
LAD and NAD
- LAD: Lamina-associated, H3 histone-enriched.
- NAD: Nucleolar-associating domains.
Nucleosome Structure
- Basic Structure: 2x4 histones (H2A, H2B, H3, H4), DNA wrapped twice, linker DNA, histone tail outside.
- During Transcription: DNA slides to expose segments, controlled by histone modifications.
Architectural Proteins
- Role: Regulate chromatin structure via DNA interactions, conserved across eukaryotes.
- Examples: Histones, Chromatin remodeling enzymes, Zinc finger proteins, Cohesins.
Epigenetics
- Definition: Genetic expression changes without DNA sequence alteration.
- Mechanisms: DNA methylation, Histone modification (mainly H3).
Nucleolus
- Composition: 10 nucleolar organizers, contains DNA, rRNA, enzymes, ribosome components.
- NOR: Contains RNA gene copies, part of chromosomes with NOR.
Centromere and Kinetochore
- Centromere: Divides chromosome into P (short) and Q (long) arms.
- Kinetochore:
- Disc-shaped protein at the chromatin duplication site.
Telomeres:
- Function: Protect chromosomes from damage or fusion, composed of repeated nucleotide sequences.