Nature: Reveals the mechanisms by which chromosomal regulation leads to the production of diverse antibodies

November 19, 2020 // --- We need various types of antibodies to help protect against foreign pathogens, and our genomes have been carefully adapted to produce these antibodies to meet emerging needs.
in a new study, researchers from research institutions such as the National Institutes of Health (NIH), Boston Children's Hospital and Harvard Medical School found that not only our DNA, but also its structure and packaging, help us produce diverse antibodies.
study was recently published in the journal Nature under the title "CTCF orchestrates long-range cohesion-driven V(D) J recombinational scanning".
and Dr. Frederick Alt and Dr. Ba Zhaoqing of Boston Children's Hospital and Dr. Rafael Casellas of the National Institutes of Health.
photo from Sebastian Stankiewicz, Boston Children's.
DNA strands are assembled with certain proteins into chromosomes.
in the new study, the authors reveal new mechanisms for chromosomal regulation ---modes the structure and packaging of our DNA--- and how this affects antibody formation and gene regulation.
they confirmed that as a protein complex that plays a major role in assembling chromatin, cohesin is also the key to forming new rings in chromatins containing fragments of different antibody genes that are longer apart.
As Alt Labs discovered earlier, this loop extrusion is essential for the V(D) J recombination process, in which V(D) J recombination brings different pieces of the genetic code together from a distance to form new antibodies.
"There has been a lot of discussion about whether adhesive proteins are really a protein complex responsible for the main process of assembling mammalian genomes into rings, and the resulting rings may be important for gene regulation, including antibody genes," said Alt, who promotes ring structure formation.
", these ring structures physically locate fragments of genes that are supposed to work together, increasing their ability to function together in series.
the ring extrusion process between adhesive proteins stops only when they encounter an obstacle called a CTCF binding element (CBE).
CBE helps separate the entire genome into clearly defined ring structures.
Ciscous protein and V(D)J recombination result in a variety of antibody types for V(D) J recombination, where the adhesive protein is located at a point in the DNA but somehow pulls past hundreds of gene fragments that are usually scattered over the chromatin.
this process led to the production of a large antibody bank.
we don't have a diverse antibody bank, we have immunodeficiency and can die, especially in the face of current epidemics," Alt explained. "Until then, we don't understand how our immune system cells find these different gene fragments in long-range chromatin, pick them out, and put them together to form a very diverse antibody bank,"
said.
paper solves another important mystery in chromatin biology: How does adhesive proteins cross CBE barriers on chromatin and naturally prevent the formation of ring structures that span longer distances? "We found that turning off CBE allowed the adhesive protein to move chromosomes in larger areas, connecting gene fragments together," Ba said.
this ultimately allows the V(D) J recombinant complex to collect and assemble these important gene fragments, which are necessary to produce a very broad antibody library.
new forms of gene regulation, their research is of greater significance than producing antibody diversity.
it points to potential new mechanisms to explain long-range gene regulation in health and disease.
Alt said, "Silent CBE blocks activity and allows adhesive proteins to pull long fragments of chromosomes together may be important for the regulation of many types of genes."
our study provides an important step in understanding a new form of gene regulation at the chromatin structure and chromatin biology level, which may be important for all forms of gene regulation.
" (Bioon.com) Reference: 1. Zhaoqing Ba et al. CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning. Nature, 2020, doi:10.1038/s41586-020-2578-0.2.Chromatin regulation enables generation of diverse antibodies。