Scientists should pursue a strategic approach to research, focusing on the accumulation of evidence via designed sequences of studies.
Image credit: Dave Cutler (artist).
New Research In
Physical Sciences
Featured Portals
Articles by Topic
Biological Sciences
Featured Portals
Articles by Topic
In PNAS, Zhang et al. (1) report the discovery of the insulator function of a cluster of CTCF-binding elements (CBEs) that defines the 3′-boundary of the immunoglobulin (Ig) heavy (H) chain locus and regulates IgH class switch recombination (CSR) (Fig. 1). This study not only resolves uncertainties surrounding the functional relevance of these CBEs in CSR (2, 3) but further strengthens a “cohesion-mediated chromatin loop extrusion” model put forth in paradigm-shifting studies from the same investigators (4⇓–6). The CSR loop extrusion model postulates a “recombination center” composed minimally of Sµ, the synapsed donor switch (S) region, and a group of enhancers located at the 3′ end of the IgH locus. Cohesion-mediated chromatin extrusion within this ∼200-kb loop is responsible for recruiting a transcription-activated acceptor switch region into the recombination center to participate in CSR (5). This model has broadly applicable implications—beyond the realm of antigen receptor gene rearrangements (both V(D)J recombination and CSR)—as it is likely applicable to many biological processes that involve long-range chromatin dynamics.
Fig. 1.
A cluster of CBEs at the 3′ boundary of IgH locus regulate cohesion-mediated chromatin loop extrusion and CSR. In wild-type (WT) cells, the 3′IgH CBEs function as an insulator to restrict transcription activation by the 3′IgHRR and cohesion-mediated chromatin extrusion. In 3′IgH CBEs-deleted (∆) cells, 3′IgHRR spreads transcription activation in downstream regions, resulting in cohesion loading, chromatin extrusion, and generation of an eS region to participate in aberrant recombination.
CSR is initiated by the B cell-specific enzyme activation-induced cytidine deaminase (AID), and …
↵1Email: yuke{at}msu.edu.
Log in using your username and password
Log in through your institution
You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.
Purchase access
You may purchase access to this article. This will require you to create an account if you don't already have one.
An insulator that regulates chromatin extrusion and class switch recombination
Sign up for Article Alerts
Article Classifications
- Biological Sciences
- Immunology and Inflammation
Jump to section
You May Also be Interested in
Despite myriad challenges, clinicians see room for progress.
Image credit: Shutterstock/David Tadevosian.
Sneaky intracellular bacteria know when to defend themselves and multiply.
Image credit: Camilla Ciolli Mattioli.
Mara Reed and Michael Manga explore why Yellowstone's Steamboat Geyser resumed erupting in 2018.
A study demonstrates how two enzymes—MHETase and PETase—work synergistically to depolymerize the plastic pollutant PET.
Image credit: Aaron McGeehan (artist).
See related content: