The 3D Organization of Our Genome

Keywords: Genome, chromosome, chromatin, 3D Genome, Epigenetics
Synopsis: This video recapitulates our current understanding of genome organization in the three-dimensional space of the cell nucleus, starting from nucleosomes, which wrap 146 base pairs of DNA, all the way to entire chromosome territories that may contain hundreds of million base pairs of DNA sequence. In-between these two extremes, the hierarchical folding of the chromatin fiber into “nucleosome clutches”, “chromatin nanodomains or CNDs”, “Topologically Associating Domains or TADs” - including their mechanism of formation via loop-extrusion - and the “A and B compartments” are presented. We include below references that support and supplement what is described in our video. We stress that some of the mechanisms involved in 3D genome organization are still debated in this research field. We also include below additional videos on the subject.
Additional videos on the subject:
1 - The video linked below illustrates the “classical paradigm” of chromosome organization corresponding to the part up to 1’03’’ in our video:
- • How DNA is Packaged (A...
2 - The following videos present the loop extrusion mechanism involved in TAD formation, described starting from 2’03’’ in our video:
- • Loop Extrusion Waltz
- • How does DNA fold? The...
References to pioneer works:
1 - A selection of recent review articles that discuss further our understanding of genome architecture and its functional consequences, described starting from 1’04’’ in our video:
- www.scientific...
- doi.org/10.103...
- www.science.or...
- doi.org/10.103...
2 - A selection of key scientific articles that describe the different layers of chromosome organization presented in our video can be found on the internet at the "doi" links indicated below. Note that some of the articles requires a subscription to the respective scientific journal.
0’27’’: The Watson and Crick DNA structure, 1953:
- doi.org/10.103...
0’30’’: The Nucleosome crystal structure, 1997:
- doi.org/10.103...
0’38’’: The 30-nm chromatin fiber has been considered for a long time to be the most basic layer of higher-order chromatin compaction, being part of the classical model. Today, the 30-nm fiber appears to be more an exception than the rule and is only observed in specific cells:
- doi.org/10.101...
- doi.org/10.101...
1’23’’: Nucleosome clutches, were discovered in 2015 and confirmed in 2017 thanks to advanced microscopy methods:
- www.cell.com/a...
- doi.org/10.112...
1’37’’: Chromatin nanodomains or CNDs are globular chromatin structures of 150-300 nm size, uncovered by using various superresolution fluorescence imaging methods:
- doi.org/10.101...
- doi.org/10.103...
- doi.org/10.112...
1’50’’: Topologically Associating Domains or TADs were uncovered in 2012 by 4 different laboratories, using a next-generation sequencing-based chromosome conformation capture method called Hi-C in Drosophila, mouse and human. They were later confirmed in other species:
- doi.org/10.101...
- doi.org/10.103...
- doi.org/10.103...
- doi.org/10.101...
2’03’’: The Loop extrusion mechanism, involving Cohesin and CTCF, seems to be a key mechanism for TAD formation in mammals and is widely studied. Below, a selection of articles on the subject. Note that the exact extrusion mechanism is still under debate and probably differs from the one shown in this video:
- doi.org/10.103...
- doi.org/10.101...
- doi.org/10.101...
- doi.org/10.103...
- doi.org/10.101...
- doi.org/10.101...
- doi.org/10.101...
- doi.org/10.107...
- doi.org/10.103...
- doi.org/10.152...
2’42’’: A and B compartments were described for the first time in 2009. Later, they were confirmed by other laboratories:
- doi.org/10.112...
- doi.org/10.112...
2’54’’: Chromosome territories represent the final layer of chromosome organization. They were first observed by DNA in situ hybridization in 1985 confirmed in many species:
- doi.org/10.100...
- doi.org/10.100...
- doi.org/10.137...
- doi.org/10.110...
Enjoy chromosome biology!

[@kevinjohansson3923]

Very clean representation and narration. 10/10. It's also very fascinating and a privilege to study.

[@cavallilabvideos8738]

We are glad to hear that it was useful!

[@AshirAzeemGill]

Absolutely fantastic, thank you for making this.

[@cavallilabvideos8738]

Glad you enjoyed it! Hope to put out another one by the end of Summer !

[@MGI2]

Great things never come from the comfort zone.. We never stop innovation.!

[@josiesbuzz]

Thank you for posting this. I will spread this video around, this is absolutely fascinating to anyone in the cell bio world.

[@laloabbasi589]

Very well explined, I am very clear about the concept of genome now.

[@kamelelnaga4636]

Extraordinaire. Magnifique . Merci pour le partage.

[@chiragPatel22c]

visualization helps a lot to understand a concept!! thanks a lot!

[@cavallilabvideos8738]

Glad it was helpful and all the best!

[@user-zd7ns9ij5g]

Beautiful and crisp.

[@midnightrumi]

Well that was a lot to unpack 🥁😂

[@asutoshrouta5724]

Great work. Thanks

[@tina9753]

Fantastic video! Thanks!😊

[@cavallilabvideos8738]

Thank you Tina, I'm glad it's useful! All the best, giacomo

[@furkankurtoglu_sys_bio]

Great video! Thank you!

[@manuelargos]

Superb

[@user-tv5sj7pt2c]

Excellent 👍

[@ccurrivan]

Thanks for posting this, it helps clarify the scales involved. One question I haven't been able to find an answer to: Is it known whether the larger chromatin structures are anchored in place by actin filaments?

[@kaviyarasisivaraman9688]

Very useful. thank you

[@dr.abdullah.noman.]

7176D

[@RollingTree2]

Excellent video! Clear/straightforward/concise visualization of these different levels of organization. Beautifully done ...thank you for sharing! One thing I didn't understand though, (if anybody can enlighten this layman), ...the highest level noted, "chromosone territory", is said to correspond to entire chromosones, but the visual shows what I presume are those seperate entire chromosones, (represented as different colors), as amorphus blobs smushed against each other. Why do we not see the typical seperate "X" shapes of each seperate chromosone commonly seen under a microscope? Am I misinterpreting something?

[@cavallilabvideos8738]

Very good question! The X shapes are a special, highly condensed state of chromosomes which is only present as the cells are diving, in the process known as mitosis. This "X"' state is optimum for neatly segregating chromosomes into daughter cells without mistakes, but it is so condensed that it is incompatible with other functions such as transcription into RNA or duplication of the DNA that is required before the cells can divide. During the remaining time of the cell life outside mitosis, when the cell is functioning, producing proteins and metabolites that maintain our body function, chromosomes partially decondense and they are no longer visible with this X shape but take the form of the pseudo globular chromosome territories depicted in the video. You can take a look at the education video: kzbin.info/www/bejne/nZO2enWee9yEatU. The first 30 seconds show folding into nucleosomes and are correct. From 30 seconds to 1minute 15 seconds they model the folding of nucleosomes into chromatin fibers, and this is the part that needed to be corrected, which we did with our video. After 1 minute 15 seconds you see the X-shaped chromosomes in mitosis and then you see how they decondense under the microscope in a time-lapse video of a cell mitosis. Hope this helps!

[@RollingTree2]

​@@cavallilabvideos8738 Thank you ...extremely helpful! Your explanation makes it all very clear, and I see that "X" state is indeed noted as very temporary/mitosis only in the other video you noted. Fascinating! These 3d visualizations are such an incredibly wonderful/powerful clarification tool!! So many aspects/details/contextual elements come to light that otherwise would be hazy or out of mind. (Though I suppose there are also numerous secondary aspects that must still be speculative in such inherently comprehensive/literal/thorough/detailed representations, (such as the particular motions for example perhaps). Regardless ...much better to have reasonable speculative placeholder secondary aspects to fill out a full picture.) Really appreciate what you do and share!!

[@_sitharam_arts]

I have one doubt i.e is it helpful for the recombinant DNA technology (the new paradigm) can any one tell me plzz..,

[@cavallilabvideos8738]

Yes it is. Indeed, a frequent observation when inserting DNA sequences into the genome in order to express proteins is that the DNA can not be expressed, or is initially expressed but mRNA expression becomes silenced over time. This is frequently due to the packaging of chromosomal DNA into condensed structures. Therefore, understanding the 3D folding of chromosomes allows one to improve DNA technologies in order to enable better and more stable expression of desired genes.

[@belkacemmeghzouchene5679]

Who did put information in DNA? Sequences are body of intelligent information. Junk DNA? But there is no junk phenotype

[@aj-uo3uh]

The genes for the heavy and light chains of immunoglobulin are in chromosome 2, 14 and 22. I was wondering if these chromosomes are neighboring each other in the nucleus and specifically in the b-cell. In this nice animation I see that the chromosomes are colored. Is there a map between the colors and the chromosomes?

[@cavallilabvideos8738]

Great question and I can not answer but the 3D organization of the B-cell genome was studied in this paper: www.nature.com/articles/s41467-020-20849-y. You might contact the corresponding authors José Martine-Subero at [e-mail] or Marc Marti-Renom @ [e-mail] for more infos!

[@alexlenail1704]

Who did the animation?

[@cavallilabvideos8738]

It is a company called Arkitek Scientific, www.arkitek.com/ ! Excellent people, we had lots of discussions with them in order to get the concepts straight and then to refine them in order to be precise and improve the rendering, they were responsive and efficient throughout the process !

[@ArayomboSolomon]

❤❤

[@noriandpets]

Is this animation based on actual microscopic or other images/ footage or just a theory?

[@cavallilabvideos8738]

Dear Nori, you will find in the discussion detailed information and further readings on many data that converge toward the interpretation that is showed in the video. Nevertheless, putting together experimental evidence on subjects of sizes that are over a million fold smaller than a centimeter (1-10 nanometer) is always a difficult and uncertain challenge and probably we will have to change several points as the knowledge progresses in the coming years. Stay tuned ...

[@noriandpets]

@@cavallilabvideos8738 Thank you!

[@sampled2291]

So it is just a big mess.