DNA Structure, Chromatin, and Genome Organization
From the Double Helix to the Nucleus
DNA architecture
The double helix is stabilized by hydrogen bonding, base stacking, ionic conditions, and sequence-dependent shape. Supercoiling, torsional stress, and nucleoprotein assembly strongly affect accessibility, replication, and transcription.
Chromatin vocabulary
Chromatin-associated features
Active regions
- Open chromatin
- Enriched for acetylation and active marks
- Often nucleosome depleted at promoters
Repressed regions
- Compact chromatin
- Enriched for repressive marks
- Reduced accessibility to transcription factors
Advanced perspective
Genome regulation is often governed less by linear distance than by three-dimensional proximity within topological and nuclear compartments.
Which feature is most directly associated with nucleosome-level DNA accessibility?
Histone acetylation generally reduces histone-DNA affinity and is associated with increased accessibility.
Correct answer: Histone acetylation
What is a topologically associating domain, or TAD?
TADs organize local regulatory interactions and can constrain enhancer-promoter communication.
Correct answer: A genomic region with frequent internal chromatin contacts relative to surrounding regions
Methods for chromatin and genome architecture
| Method | What it reveals |
|---|---|
| ATAC-seq | Open chromatin |
| ChIP-seq | Protein-DNA binding or histone marks |
| Hi-C | Genome-wide contact frequencies |
| MNase-seq | Nucleosome positioning |
| CUT&RUN | Targeted chromatin profiling with low background |
What is the primary advantage of Hi-C over a simple locus-specific assay?
Hi-C maps chromatin interactions across the genome, enabling analysis of compartments, loops, and TADs.
Correct answer: It captures genome-wide contact topology
Why can changes in 3D genome organization alter gene expression without changing DNA sequence?
Spatial proximity is a major determinant of transcriptional regulation.
Correct answer: They change which regulatory elements can physically contact promoters and other control regions