The 3D Organization of Our Genome TubeRipper com

since the discovery of DNA in 1953 the question of how it organizes itself in the three-dimensional space of the cell nucleus has fascinated the research world DNA is comprised of four nucleic bases adenine thymine guanine and cytosine which specifically pair together to form the ladders along a sugar phosphate backbone creating the familiar DNA strand this strand is wrapped around histone proteins to form nucleosomes which in turn were thought to form more complex structures that neatly pack the DNA into Loosely coiled structures which in turn would be finally packed into structures called chromosomes apart from the difficulty of reading DNA sections wound in this manner the subsequent folding path between the nucleosome and chromosome territories was unclear and was represented schematically as bundles of spaghetti-like fibers however new genomic and imaging techniques have allowed our lab and other Laboratories to finally understand what the organizational structure actually is in this new model the organization of DNA at the nucleosome level remains unchallenged but from here on out things change nucleosomes do not assemble into an ordered symmetrical structure but rather into loose unordered groupings of nucleosomes called clutches each containing a small number of nucleosomes these clutches group together to form a new structure defined as chromatin nanodomains or cnds which include about 100 to 200 000 base pairs of DNA the next level of organization is called tads or topologically associating domains which include variable amounts of DNA with an average of about one megabase in size tads are highly heterogeneous structures notably due to the dynamic mechanism of their formation by Loop Extrusion involving the cohesion complex and ctcf in mammals strings of nucleosomes are pulled through the cohesion complex until cohesive income counters the borders occupied by ctcf this process of loop Extrusion abruptly halts when the cohesion complex meets convergently oriented ctcf factors present at Tad borders this Tad formation preserves specific Gene regions in their local groupings tads become grouped into two distinct compartments the a compartment which mainly contains active genes and the B compartment including mainly inactive genes the final level of this organization is the chromosome territory this level corresponds to an entire chromosome which occupies its own space within the nucleus with reduced intermingling with the other chromosomes the progress made in the last decade has filled the knowledge Gap that existed between the nucleosome and the chromosome territory this no structural Paradigm solves many problems inherent in the classical model and is Paving the way towards a better understanding of Gene regulation in normal cells and in disease [Music]

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Length: 3min 41sec (221 seconds)

Published: Fri Dec 09 2022