Chromatin, Epigenetics, and 3D Genome Organization
Chromatin as a regulatory substrate
Nucleosomes and accessibility
Eukaryotic DNA is packaged into nucleosomes, each containing approximately base pairs wrapped around a histone octamer. Chromatin compaction is not merely structural; it defines accessibility, recruitment of transcription factors, replication timing, DNA repair, and developmental state.
Common epigenetic marks
3D genome folding
Chromosomes occupy territories and are organized into compartments, topologically associating domains, and enhancer-promoter contact networks. The mechanistic role of loop extrusion, cohesin, CTCF, transcription, and phase separation remains a frontier problem in genome regulation.
Open problem
One major unresolved question is how much of gene regulation is encoded in static DNA sequence versus emergent from dynamic chromatin state and nuclear architecture.
Euchromatin vs heterochromatin
Euchromatin
- More transcriptionally permissive
- Generally higher accessibility
- Enriched for active marks
Heterochromatin
- More compact and repressive
- Often late-replicating
- Associated with silencing and structural organization
Which feature is most strongly associated with active enhancer regions?
H3K27ac is a classic mark of active enhancers.
Correct answer: H3K27ac
What is a topological associating domain, or TAD?
TADs are a useful structural unit for studying gene regulation and enhancer specificity.
Correct answer: A genomic region with elevated internal chromatin interactions relative to neighboring regions
Which process is most directly implicated in nucleosome repositioning?
Chromatin remodelers use ATP to reposition or evict nucleosomes.
Correct answer: ATP-dependent chromatin remodeling
State one mechanistic hypothesis for how chromatin loops can influence transcription.
Looping can facilitate contact-dependent recruitment of transcriptional machinery.
Correct answer: They bring enhancers and promoters into proximity