๐งฌ Chromatin is the complex of DNA + proteins within the eukaryotic nucleus.
Its primary role is to package DNA into compact structures, allowing for DNA storage, replication, repair, and gene regulation.
The state of chromatin (open vs condensed) directly influences gene expression and cell behaviour.
๐ Components of Chromatin
- DNA ๐งพ : Genetic material encoding all cellular proteins and functions.
- Histones ๐ : Core proteins (H2A, H2B, H3, H4) form nucleosome cores; H1 stabilises linker DNA. Histone modifications regulate gene activity.
- Non-histone Proteins โ๏ธ : Transcription factors, chromatin remodelling complexes, polymerases, DNA repair proteins.
๐๏ธ Structure of Chromatin
- Nucleosome ("beads-on-a-string") : 147 bp of DNA wrapped around histone octamer (H2A, H2B, H3, H4). Linked by H1.
- 30 nm Fibre : Higher-order coiling of nucleosomes; stabilised by H1 and scaffold proteins.
- Looped Domains : Chromatin loops anchored to scaffold/matrix โ forms visible chromosomes during mitosis.
๐ Types of Chromatin
- Euchromatin ๐ : Less condensed, transcriptionally active, rich in gene expression. Found in regions with actively transcribed genes.
- Heterochromatin ๐ : Densely packed, transcriptionally silent. Often repetitive DNA (centromeres, telomeres, Barr body in females).
โ๏ธ Functions of Chromatin
- DNA Packaging ๐ฆ : Compacts ~2 metres of DNA into the tiny nucleus.
- Gene Regulation ๐ : Accessibility controlled by histone modifications (acetylation, methylation) and DNA methylation.
- DNA Replication ๐ : Chromatin loosens during S phase to allow polymerase activity.
- DNA Repair ๐ ๏ธ : Local chromatin remodelling required for repair enzymes to access damaged DNA.
- Cell Division โก : Chromatin condenses into chromosomes during mitosis & meiosis for faithful segregation.
๐งช Clinical Relevance
- Chromatinopathies โ ๏ธ : Mutations in chromatin-remodelling genes โ developmental syndromes (e.g. Rett syndrome, ATRX-related disorders).
- Cancer ๐งจ : Aberrant DNA methylation & histone modifications โ silencing tumour suppressors, activating oncogenes.
- Neurodegeneration ๐ง : Epigenetic dysregulation linked with Alzheimerโs, Huntingtonโs disease.
- Epigenetics ๐ฌ : Heritable changes in gene expression without DNA sequence change.
- Histone acetylation โ gene activation.
- Histone methylation โ activation or repression (context-dependent).
- DNA methylation (CpG islands) โ gene silencing.
๐ Summary
Chromatin is the dynamic DNAโprotein complex that enables compaction, regulation, and protection of the genome.
It exists in two forms: Euchromatin (open, active) and Heterochromatin (condensed, silent).
Disruptions in chromatin organisation underpin major diseases including cancer, neurodegeneration, and congenital syndromes, making it central to both cell biology and clinical medicine.