Abstract
Senigl et al. show that genome susceptibility to somatic hypermutation (SHM) is confined within topologically associated domains (TADs) and is linked to markers of strong enhancers and stalled transcription and high levels of the cohesin loader NIPBL. Insertion of an ectopic SHM targeting element renders an entire TAD susceptible to SHM.
Original language | English |
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Pages (from-to) | 3902-3915.e8 |
Journal | Cell Reports |
Volume | 29 |
Issue number | 12 |
DOIs | |
State | Published - 17 Dec 2019 |
Externally published | Yes |
Bibliographical note
Funding Information:The authors thank Zdenek Cimburek for help with cell sorting and Richard Frock for instruction in the use of HTGTS. This work was supported in part by grant R01 AI127642 (D.G.S.), grant 15-24776S from the Czech Science Foundation (F.S.), Praemium Academiae of the Czech Academy of Science (J.H.), the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases ( NIAMS ) and the National Institutes of Health ( NIH ) (R.C.), a Gruber Science Fellowship and National Science Foundation Graduate Research Fellowship (R.D.), and grants from the Sigrid Juselius Foundation , the Jane and Aatos Erkko Foundation , the Jenny and Antti Wihuri Foundation , the Ella and Georg Ehrnrooth Foundation , the Cancer Society of South-West Finland , and the Emil Aaltonen Foundation (J.A.).
Funding Information:
The authors thank Zdenek Cimburek for help with cell sorting and Richard Frock for instruction in the use of HTGTS. This work was supported in part by grant R01 AI127642 (D.G.S.), grant 15-24776S from the Czech Science Foundation (F.S.), Praemium Academiae of the Czech Academy of Science (J.H.), the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Institutes of Health (NIH) (R.C.), a Gruber Science Fellowship and National Science Foundation Graduate Research Fellowship (R.D.), and grants from the Sigrid Juselius Foundation, the Jane and Aatos Erkko Foundation, the Jenny and Antti Wihuri Foundation, the Ella and Georg Ehrnrooth Foundation, the Cancer Society of South-West Finland, and the Emil Aaltonen Foundation (J.A.). F.S. Y.M. R.K.D. J.A. J.-M.B. R.C. J.H. and D.G.S. designed experiments. F.S. Y.M. R.K.D. J.A. R.B.S. L.P. A.D.O. S.S.P.R. and D.W. performed experiments. F.S. Y.M. R.K.D. J.A. R.B.S. E.L.A. R.C. J.H. and D.G.S. analyzed the data. F.S. and D.G.S. wrote the manuscript with input from the other authors. The authors declare no competing interests.
Publisher Copyright:
© 2019 The Authors
Keywords
- activation induced deaminase
- chromatin loop extrusion
- chromatin structure
- somatic hypermutation
- topologically associated domain
- transcription factor