Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

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

doi:10.1016/j.celrep.2019.11.039

Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

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

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25 Scopus citations

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
Pages (from-to)	3902-3915.e8
Journal	Cell Reports
Volume	29
Issue number	12
DOIs	https://doi.org/10.1016/j.celrep.2019.11.039
State	Published - 17 Dec 2019
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2019 The Authors

Funding

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.). 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.

Funders	Funder number
Cancer Society of South-West Finland
Praemium Academiae of the Czech Academy of Science
Sigrid Juselius Foundation
National Science Foundation
National Institutes of Health
National Institute of Allergy and Infectious Diseases	R01AI127642
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Grantová Agentura České Republiky
Ella ja Georg Ehrnroothin Säätiö
Jane ja Aatos Erkon Säätiö
Jenny ja Antti Wihurin Rahasto
Emil Aaltosen Säätiö
Lounais-Suomen Syöpäyhdistys
Sigrid Juséliuksen Säätiö

Keywords

activation induced deaminase
chromatin loop extrusion
chromatin structure
somatic hypermutation
topologically associated domain
transcription factor

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10.1016/j.celrep.2019.11.039

Cite this

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title = "Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation",

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.",

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AU - Pecnova, Lubomira

AU - Omer, Arina D.

AU - Rao, Suhas S.P.

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AU - Buerstedde, Jean Marie

AU - Aiden, Erez Lieberman

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AU - Hejnar, Jiri

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Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

Abstract

Bibliographical note

Funding

Keywords

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