The DSIF subunits Spt4 and Spt5 have distinct roles at various phases of immunoglobulin class switch recombination.

PLoS Genetics
Andre StanlieTasuku Honjo

Abstract

Class-switch recombination (CSR), induced by activation-induced cytidine deaminase (AID), can be divided into two phases: DNA cleavage of the switch (S) regions and the joining of the cleaved ends of the different S regions. Here, we show that the DSIF complex (Spt4 and Spt5), a transcription elongation factor, is required for CSR in a switch-proficient B cell line CH12F3-2A cells, and Spt4 and Spt5 carry out independent functions in CSR. While neither Spt4 nor Spt5 is required for transcription of S regions and AID, expression array analysis suggests that Spt4 and Spt5 regulate a distinct subset of transcripts in CH12F3-2A cells. Curiously, Spt4 is critically important in suppressing cryptic transcription initiating from the intronic Sμ region. Depletion of Spt5 reduced the H3K4me3 level and DNA cleavage at the Sα region, whereas Spt4 knockdown did not perturb the H3K4me3 status and S region cleavage. H3K4me3 modification level thus correlated well with the DNA breakage efficiency. Therefore we conclude that Spt5 plays a role similar to the histone chaperone FACT complex that regulates H3K4me3 modification and DNA cleavage in CSR. Since Spt4 is not involved in the DNA cleavage step, we suspected that Spt4 might be required for...Continue Reading

References

Jan 1, 1981·Molecular & General Genetics : MGG·M Ciriacy, V M Williamson
Apr 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·G SimchenG R Fink
Feb 11, 1993·Nucleic Acids Research·W DunnickC Gritzmacher
Feb 1, 1996·International Immunology·M NakamuraT Honjo
May 26, 1998·The EMBO Journal·R CasellasM C Nussenzweig
Oct 29, 1999·Genes & Development·A J PierceM Jasin
Jan 10, 2002·The Journal of Experimental Medicine·Rodrig MarculescuBertrand Nadel
Feb 28, 2002·Annual Review of Immunology·Tasuku HonjoMasamichi Muramatsu
Mar 8, 2002·Current Biology : CB·Reuben S HarrisMichael S Neuberger
Oct 23, 2002·Molecular and Cellular Biology·Xianming Mo, William S Dynan
Jun 5, 2003·Genes & Development·Chwen-Huey WuDavid Gilmour
Jan 20, 2005·The Journal of Experimental Medicine·Qiang Pan-HammarströmMichael R Ehrenstein
Jun 23, 2005·Nature Immunology·Tasuku HonjoMasamichi Muramatsu
Aug 17, 2005·The Journal of Experimental Medicine·Carol E SchraderJanet Stavnezer
Jun 30, 2006·DNA Repair·Albino BacollaRobert D Wells
Nov 23, 2007·Nature·Adam G W MatthewsMarjorie A Oettinger
Dec 25, 2007·Nature Structural & Molecular Biology·Kira Glover-CutterDavid L Bentley
Jan 12, 2008·The Journal of Biological Chemistry·Ming Zhang, Patrick C Swanson
Feb 21, 2008·Nature Reviews. Molecular Cell Biology·Dana Branzei, Marco Foiani
Sep 23, 2008·Epigenetics : Official Journal of the DNA Methylation Society·Ian M FingermanScott D Briggs
Nov 22, 2008·Nature Reviews. Molecular Cell Biology·Philip C Hanawalt, Graciela Spivak

❮ Previous
Next ❯

Citations

Sep 26, 2012·The Journal of Experimental Medicine·Katharina L WillmannSvend K Petersen-Mahrt
Apr 24, 2013·Proceedings of the National Academy of Sciences of the United States of America·Masatoshi AidaTasuku Honjo
Nov 28, 2012·Autoimmunity·Elisabetta IncorvaiaKerstin-Maike Schmitz
Jul 31, 2012·Seminars in Immunology·Kerstin-Maike Schmitz, Svend K Petersen-Mahrt
Sep 18, 2012·Biochimica Et Biophysica Acta·Grant A Hartzog, Jianhua Fu
Mar 15, 2018·Frontiers in Immunology·Emily C SheppardRichard Chahwan
Sep 20, 2020·Nature Communications·Elisabeth Anne Adanma ObaraPetra Hamerlik
Sep 29, 2020·Journal of Molecular Biology·Tim-Michael Decker

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE33206
AC073553
D11468

Methods Mentioned

BETA
deamination
flow cytometry
gene knockdown
FACS
ChIP
PCR
ubiquitination
transfection
immunoprecipitation

Related Concepts

Related Feeds

B cells: Gene Expression

B lymphocytes are white blood cells that play a role in the adaptive immune system by secreting antibodies. Here is the latest research on gene expression in B cells.