This is indeed a controversial field, with some publications supporting the existence of inheritance through multiple generations, mostly in mouse, despite the reset waves. A number of scientists remain skeptical and evoke confounding parameters affecting the published results. We published a review on the subject, see pubmed.ncbi.nlm.nih.gov/34983971/. The two best papers to my knowledge supporting transgenerational inheritance (published after our review) are from the Izpisua-belmonte lab: DOI: 10.1016/j.cell.2022.12.047 and from the Terranova lab www.nature.com/articles/s41467-023-41998-w (although this last one shows inheritance of gene expression changes, not of a phenotype). The best paper arguing against this phenomenon in mouse is from the Ferguson-Smith lab: DOI: 10.1016/j.cell.2018.09.043. In sum, I think the jury is out and there might be cases of transgenerational inheritance, although relatively rare. All this of course is very difficult to study in human. Nevertheless, I hope this information is helpful.

@@cavallilabvideos8738 nice. Thanks for the links. I’ll check them out when I have time. My concern with this topic is that there are many influencers (usually the ones without a strong scientific background, and who focus on culture and societal implications at large) who state with complete confidence that this is 100% factual knowledge, which clearly it is not, and likely plays a nominal role. The extrapolation is insane. I saw one with Neil Degreese who was learning about it from someone who discussed behavioral observational data at best, but clearly doesn’t understand the epigenetic changes on a molecular level. The comment sections were riddled with people discussing how white people are responsible for numerous cultural problems with African Americans and the blame game was everywhere. The horse is out of the barn. I’ve heard some podcasters affirm the fact that men in certain cultures like certain body types due to epigenetic changes in ancestors that have been passed down, like it wasn’t possible to simply be a cultural preference, which is obviously is. In other words, parental and generational influence on children such as thought patterns, speech patterns etc are by far most likely due to learned behaviors and there is zero evidence that it’s from changes that affect gene expression, and a LOT of evidence that it isn’t.

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.

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

We published a review specifically on this subject - see www.nature.com/articles/s41576-021-00438-5

Thanks a lot, we'll go for it nex year! All the best

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!

​@@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!!

Glad it was helpful and all the best!

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 ...

@@cavallilabvideos8738 Thank you!

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

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 [email protected] or Marc Marti-Renom @ [email protected] for more infos!

Yes, H3K27Acetylation will prevent PRC2 to deposit H3K27 methylation by direct competition and so H3K27Ac blocks silencing. Furthermore, H3K36 di- or trimethylation inhibits PRC2. see article DOI: 10.7554/eLife.61964 for an explanation of the mechanism.

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 !

We are glad to hear that it was useful!

Yes, nucleosome clutches were first observed by Maria Aurelia Ricci and colleagues in 2015, using the incorporation of a fluorescent histone into the chromatin fiber and its observation with Stochastic Optical Reconstruction Microscopy (STORM, see link 1- below), an advanced fluorescence microsopy method that provides extremely high spatial resolution. These small nucleosome aggregates were confirmed by Ou and colleagues, using ChromEMT, which combines "multitilt electron microscopy tomography" with a labeling method to selectively enhance the DNA contrast (again, advanced microscopy methodology, see link 2- below). These nucleosome aggregates represent a disordered 5- to 24-nm-diameter curvilinear chain that can be further packed inside interphase nuclei: 1- www.cell.com/action/showPdf?p... 2- doi.org/10.1126/science.aag0025