Nuclear Organization

Question 1

What is a reason that certain translocation types are much more likely to occur in specific cell types?

Answer 1

Chromosomes occupy very specific chromosomal territories in different cell types and thus will almost always neighbour the same regions of other neighbouring chromosomes. This translocates those regions much more likely in the given cell type. This allows us to determine cell types of cancers if translocations like this are present.

Question 2

TADs?

Answer 2

Topologically Associated Domains- regions of a chromosome that tend to stay close to eachother aka topologically associated

Question 3

How do you determine TADs

Answer 3

Hi-C: comprehensively detects genome-wide chromatin interactions in the cell nucleus by combining 3C and next-generation sequencing (NGS) approaches and has been considered as a qualitative leap in C-technology (chromosome conformation capture-based technologies) development and the beginning of 3D genomics. (wiki)

Hi-C maps visualize TADs, x and y axis are the seq position on a chromosome an intensity of color represents how close they are. Thus TADs can generally be seens as squares of high activity. Some sub-squares can also be visible.

Question 4

Types of TADs

Answer 4

A (active) and B (inactive/blocked?) compartments

Ordinary and Loop domains (the second being a product of loop extrusion)

Question 5

Describe loop extrusion

Answer 5

Ahh cohesins pull DNA loop until they reach CTCFs see a video if you forgot.

Question 6

What happens if you delete the Tsix-Xist boundary region.

Answer 6

These two generally seperate TADs will have much more interactions between eachother as this region is an insulator on which CTCF would bind.

Question 7

If a TAD is very close to the nuclear lamina is it more likely that it is A or B

Answer 7

repressed (B), LADs

Question 8

NADs?

Answer 8

Nucleolus Associated Domains -> the rRNA genes

Question 9

What is the activity of genes in the nucleouls?

Answer 9

High in the inside and low in the periphery

Question 10

The Transcription Factory hypotheis

Answer 10

Transcription Factors, RNA pol assemble in high local concentrations in specific region. Thus when regions of chromosomes have to be expressed they are moved towards those Transcription factories. Centralised hotspots of transcription

Question 11

If a region of a chromosome is close to the NPC what does that tell us about it activity.

Answer 11

Active, mRNA can diffuse out of the nucleus more easily.