Skip to Content
MilliporeSigma
  • Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation.

Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation.

Cell reports (2019-12-19)
Filip Senigl, Yaakov Maman, Ravi K Dinesh, Jukka Alinikula, Rashu B Seth, Lubomira Pecnova, Arina D Omer, Suhas S P Rao, David Weisz, Jean-Marie Buerstedde, Erez Lieberman Aiden, Rafael Casellas, Jiri Hejnar, David G Schatz
ABSTRACT

Somatic hypermutation (SHM) introduces point mutations into immunoglobulin (Ig) genes but also causes mutations in other parts of the genome. We have used lentiviral SHM reporter vectors to identify regions of the genome that are susceptible ("hot") and resistant ("cold") to SHM, revealing that SHM susceptibility and resistance are often properties of entire topologically associated domains (TADs). Comparison of hot and cold TADs reveals that while levels of transcription are equivalent, hot TADs are enriched for the cohesin loader NIPBL, super-enhancers, markers of paused/stalled RNA polymerase 2, and multiple important B cell transcription factors. We demonstrate that at least some hot TADs contain enhancers that possess SHM targeting activity and that insertion of a strong Ig SHM-targeting element into a cold TAD renders it hot. Our findings lead to a model for SHM susceptibility involving the cooperative action of cis-acting SHM targeting elements and the dynamic and architectural properties of TADs.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Hexammine cobalt(III) chloride, for use in transformations, X-ray crystallography and NMR
Sigma-Aldrich
Anti-YY2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody