Publication Date:
2010-07-31
Description:
Programmed genetic rearrangements in lymphocytes require transcription at antigen receptor genes to promote accessibility for initiating double-strand break (DSB) formation critical for DNA recombination and repair. Here, we showed that activated B cells deficient in the PTIP component of the MLL3 (mixed-lineage leukemia 3)-MLL4 complex display impaired trimethylation of histone 3 at lysine 4 (H3K4me3) and transcription initiation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus, leading to defective immunoglobulin class switching. We also showed that PTIP accumulation at DSBs contributes to class switch recombination (CSR) and genome stability independently of Igh switch transcription. These results demonstrate that PTIP promotes specific chromatin changes that control the accessibility of the Igh locus to CSR and suggest a nonredundant role for the MLL3-MLL4 complex in altering antibody effector function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008398/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008398/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Daniel, Jeremy A -- Santos, Margarida Almeida -- Wang, Zhibin -- Zang, Chongzhi -- Schwab, Kristopher R -- Jankovic, Mila -- Filsuf, Darius -- Chen, Hua-Tang -- Gazumyan, Anna -- Yamane, Arito -- Cho, Young-Wook -- Sun, Hong-Wei -- Ge, Kai -- Peng, Weiqun -- Nussenzweig, Michel C -- Casellas, Rafael -- Dressler, Gregory R -- Zhao, Keji -- Nussenzweig, Andre -- Z01 AR041149-03/Intramural NIH HHS/ -- Z01 AR041149-04/Intramural NIH HHS/ -- Z01 DK047055-01/Intramural NIH HHS/ -- Z01 DK047055-02/Intramural NIH HHS/ -- Z01 DK075003-04/Intramural NIH HHS/ -- Z01 DK075003-05/Intramural NIH HHS/ -- Z99 DK999999/Intramural NIH HHS/ -- ZIA AR041149-05/Intramural NIH HHS/ -- ZIA DK075017-03/Intramural NIH HHS/ -- ZIADK047055-03/DK/NIDDK NIH HHS/ -- ZIADK075003-06/DK/NIDDK NIH HHS/ -- ZIADK075017-01/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Aug 20;329(5994):917-23. doi: 10.1126/science.1187942. Epub 2010 Jul 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Immunology Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20671152" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibody Specificity/genetics
;
Carrier Proteins/genetics/*physiology
;
Cytidine Deaminase/metabolism
;
Dna
;
Histones/metabolism
;
Immunoglobulin Class Switching/genetics/*physiology
;
Immunoglobulin Switch Region
;
Methylation
;
Mice
;
Nuclear Proteins/genetics/*physiology
;
Promoter Regions, Genetic
;
Recombination, Genetic
;
Transcriptional Activation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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