Attracting AID to targets of somatic hypermutation.

The Journal of Experimental Medicine
Atsushi TanakaU Storb

Abstract

The process of somatic hypermutation (SHM) of immunoglobulin (Ig) genes requires activation-induced cytidine deaminase (AID). Although mistargeting of AID is detrimental to genome integrity, the mechanism and the cis-elements responsible for targeting of AID are largely unknown. We show that three CAGGTG cis-elements in the context of Ig enhancers are sufficient to target SHM to a nearby transcribed gene. The CAGGTG motif binds E47 in nuclear extracts of the mutating cells. Replacing CAGGTG with AAGGTG in the construct without any other E47 binding site eliminates SHM. The CA versus AA effect requires AID. CAGGTG does not enhance transcription, chromatin acetylation, or overall target gene activity. The other cis-elements of Ig enhancers alone cannot attract the SHM machinery. Collectively with other recent findings, we postulate that AID targets all genes expressed in mutating B cells that are associated with CAGGTG motifs in the appropriate context. Ig genes are the most highly mutated genes, presumably because of multiple CAGGTG motifs within the Ig genes, high transcription activity, and the presence of other cooperating elements in Ig enhancers.

References

Jun 1, 1994·European Journal of Immunology·C RadaC Milstein
Feb 1, 1994·Molecular and Cellular Biology·H L HsuR Baer
Feb 1, 1994·The Journal of Experimental Medicine·N MotoyamaT Azuma
Jun 1, 1993·Molecular and Cellular Biology·G BainC Murre
Sep 2, 1998·International Immunology·P Wu, L Claflin
Sep 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·L PasqualucciR Dalla-Favera
Dec 20, 2000·The Journal of Experimental Medicine·M MüschenR Küppers
Feb 24, 2001·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·U StorbN Kim
Apr 6, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J BachlC Olsson
Mar 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Melinda S GordonRandolph Wall
Feb 27, 2004·Nature Immunology·Oleg OsipovichEugene M Oltz
May 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·Clifford L WangMatthias Wabl
Jan 26, 2005·Trends in Immunology·Vasco M BarretoMichel C Nussenzweig
Mar 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ai KotaniTasuku Honjo
Jul 26, 2005·Immunity·Valerie H OdegardDavid G Schatz
Feb 9, 2006·Current Opinion in Immunology·Simonne LongerichUrsula Storb
Mar 18, 2006·Molecular Immunology·Jahan-Yar ParsaAlberto Martin
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ulrike SchoetzJean-Marie Buerstedde
Oct 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hong Ming ShenUrsula Storb
Dec 21, 2006·The Journal of Experimental Medicine·Shu Yuan YangDavid G Schatz
Jan 10, 2008·International Immunology·Hiroyuki KitaoMinoru Takata
Feb 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nagarama KothapalliSebastian D Fugmann
Jan 10, 2009·PLoS Genetics·Artem BlagodatskiJean-Marie Buerstedde

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Citations

Apr 3, 2014·PLoS Biology·Jean-Marie BuersteddeDavid G Schatz
Apr 22, 2014·Frontiers of Medicine·Zhangguo Chen, Jing H Wang
Apr 22, 2014·Molecular Immunology·Anders WalleniusThomas Grundström
Jun 12, 2013·The Journal of Experimental Medicine·Prashant KodgireUrsula Storb
Nov 28, 2012·Cellular and Molecular Life Sciences : CMLS·Malgorzata JaszczurMyron F Goodman
Jan 1, 2016·DNA Repair·Kimberly J Zanotti, Patricia J Gearhart
Jul 13, 2012·Seminars in Immunology·Amy L Kenter
Jun 19, 2012·Seminars in Immunology·Richard ChahwanSergio Roa
Feb 26, 2011·Developmental and Comparative Immunology·Vasco M Barreto, Brad G Magor
Feb 8, 2011·Current Opinion in Immunology·Naga Rama Kothapalli, Sebastian D Fugmann
Aug 9, 2015·Trends in Immunology·Vivek ChandraCornelis Murre
Nov 12, 2016·Molecular Immunology·Jannek HauserThomas Grundström
Dec 11, 2019·European Journal of Immunology·Ravi K DineshDavid G Schatz
Sep 11, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhangguo ChenJing H Wang
Sep 15, 2020·International Reviews of Immunology·Ankit JaiswalPrashant Kodgire
Aug 17, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Naga Rama KothapalliSebastian D Fugmann
Oct 24, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhangguo ChenJing H Wang
Sep 22, 2017·International Reviews of Immunology·Meenal ChoudharyPrashant Kodgire
Mar 22, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jamie L DukeSteven H Kleinstein
Aug 26, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ahrom KimKefei Yu
Jul 10, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica J McDonaldDavid G Schatz
Oct 23, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kristin M KohlerDavid G Schatz
Apr 10, 2021·European Journal of Immunology·David BassanLea Eisenbach

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Methods Mentioned

BETA
transgenic
ChIP
PCR
flow cytometry
FACS
immunoprecipitation
acetylation
deamination
PCRs

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