lo 1 1. How is mammalian chromatin structure organised?

What are the two main forms of chromatin originally distinguished cytologically?

Euchromatin and heterochromatin [answer] Euchromatin stains less intensely and is decondensed, while heterochromatin stains intensely due to tighter packing.

What is euchromatin?

Decondensed chromatin [answer] Euchromatin is the less intensely staining, more open form of chromatin that is generally transcriptionally active.

What is heterochromatin?

Condensed chromatin [answer] Heterochromatin is the intensely staining, tightly packed form of chromatin that is generally transcriptionally repressed.

What is a TAD?

Topologically Associating Domain [answer] TADs are genomic sequences in the range of megabases in length that are separated by boundary regions and physically interact with themselves more frequently than with the rest of the genome.

How frequent are TADs across different cell types?

60-70% of TADs are invariant [answer] A large fraction of TADs (60-70%) are almost invariant among different cell types and between species, suggesting TADs are fundamental functional units of the genome.

What are the hierarchical layers of 3D genome organisation?

Chromosome territories → A/B compartments → TADs → DNA loops [answer] DNA exists in chromosome territories, which are further divided into chromatin compartments A and B, with finer-scale structures such as TADs and DNA loops within them.

What do chromatin compartments A and B represent?

Active and repressed chromatin regions [answer] A compartments are transcriptionally active regions, while B compartments are transcriptionally repressed regions.

What technique is used to study 3D genome organisation?

Hi-C [answer] Hi-C is a genome-wide derivative that reveals each interaction in the nuclear space, resulting in a 2D heat map showing the frequency of interaction between two points in the genome.

What does a Hi-C heat map show?

Frequency of interactions between genomic regions [answer] Each data point in a Hi-C heat map indicates the frequency of interaction between two points in the genome.

What are chromosome territories?

Distinct spatial regions occupied by each chromosome in the nucleus [answer] Chromosome territories are distinct regions within the nucleus where individual chromosomes are localised, as shown by chromosome painting experiments.

Are TADs found in all species?

No, TADs are animal specific [answer] TADs are animal specific and do not exist in all species. Other organisms have sub-chromosomal mechanisms of organisation that are reminiscent of mammalian A and B compartments but are not considered TADs.

Why might TADs not be needed in single-cell organisms?

They have highly compact genomes [answer] Many single-cell organisms have highly compact genomes, so they don't need methods to improve distal enhancer-promoter contacts, making TADs unnecessary.

Where do most enhancer-promoter interactions occur?

Within TADs [answer] Most enhancer-promoter interactions occur within TADs, which form a genomic scaffold that facilitates regulatory interactions while insulating regulatory activity from neighbouring domains.

What is the approximate size of a TAD?

Megabases in length [answer] TADs are genomic sequences in the range of megabases in length.

What is CTCF in relation to TADs?

CTCF is the "insulator" protein that binds at TAD boundaries [answer] CTCF is often referred to as an 'insulator' and binds its specific DNA motif at TAD boundaries, preventing TAD 'mixing' or loss of TAD structure.

What is the Cohesin complex?

A multisubunit ring-shaped complex that coordinates TAD spatial constraints [answer] The Cohesin complex forms a ring that coordinates the spatial constraints of TADs and plays key roles in transcriptional control and 3D genome architectu