Home LiteratureArticle Details
PMID: 12196630 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Regulation of V(D)J recombination: a dominant role for promoter positioning in gene segment accessibility.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 19 ·2002-09-17 ·Pages 12309-14

Sikes ML, Meade A, Tripathi R, Krangel MS, Oltz EM

Abstract

Antigen receptor gene assembly is regulated by transcriptional promoters and enhancers, which control the accessibility of gene segments to a lymphocyte-specific V(D)J recombinase. However, it remained unclear whether accessibility depends on the process of transcription itself or chromatin modifications that accompany transcription. By using T cell receptor beta substrates that integrate stably into nuclear chromatin, we show that promoter location, rather than germ-line transcription or histone acetylation, is a primary determinant of recombination efficiency. These spatial constraints on promoter positioning may reflect an RNA polymerase-independent mechanism to target adjacent gene segments for chromatin remodeling events that facilitate rearrangement.

MeSH Terms
Acetylation Cell Line DNA Nucleotidyltransferases/genetics,metabolism DNA-Binding Proteins/genetics,metabolism Genes, Immunoglobulin Genes, RAG-1 Histones/chemistry,metabolism Homeodomain Proteins/genetics,metabolism Humans Lymphocytes/immunology,metabolism Models, Genetic Nuclear Proteins Promoter Regions, Genetic Receptors, Antigen, T-Cell, alpha-beta/genetics Recombination, Genetic Transfection VDJ Recombinases
Chemicals
DNA-Binding Proteins Histones Homeodomain Proteins Nuclear Proteins RAG2 protein, human Receptors, Antigen, T-Cell, alpha-beta V(D)J recombination activating protein 2 RAG-1 protein DNA Nucleotidyltransferases VDJ Recombinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sikes Michael L
Department of Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
Meade Amber
Tripathi Rajkamal
Krangel Michael S
Oltz Eugene M
References (37)
37 references, click to expand
  1. Germ-line transcription and methylation status of the TCR-J alpha locus in its accessible configuration.
    Eur J Immunol. 1997 Jul;27(7):1619-25 PMID: 9247569
  2. Deletion of the mouse T-cell receptor beta gene enhancer blocks alphabeta T-cell development.
    Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7877-81 PMID: 8755570
  3. Histone acetylation and transcriptional regulatory mechanisms.
    Genes Dev. 1998 Mar 1;12(5):599-606 PMID: 9499396
  4. Structure of nonhairpin coding-end DNA breaks in cells undergoing V(D)J recombination.
    Mol Cell Biol. 1998 Apr;18(4):2029-37 PMID: 9528775
  5. A role for histone acetylation in the developmental regulation of VDJ recombination.
    Science. 2000 Jan 21;287(5452):495-8 PMID: 10642553
  6. Stimulation of V(D)J recombination by histone acetylation.
    Curr Biol. 2000 Apr 20;10(8):483-6 PMID: 10801420
  7. Mechanisms that direct ordered assembly of T cell receptor beta locus V, D, and J gene segments.
    Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7975-80 PMID: 10869424
  8. Chromatin remodeling by the T cell receptor (TCR)-beta gene enhancer during early T cell development: Implications for the control of TCR-beta locus recombination.
    J Exp Med. 2000 Sep 4;192(5):625-36 PMID: 10974029
  9. Unequal access: regulating V(D)J recombination through chromatin remodeling.
    Cell. 2000 Nov 22;103(5):699-702 PMID: 11114326
  10. Deletion of germline promoter PD beta 1 from the TCR beta locus causes hypermethylation that impairs D beta 1 recombination by multiple mechanisms.
    Immunity. 2000 Nov;13(5):703-14 PMID: 11114382
  11. Transcription factor NF-kappa B regulates Ig lambda light chain gene rearrangement.
    J Immunol. 2001 Jul 1;167(1):264-9 PMID: 11418658
  12. Factors and forces controlling V(D)J recombination.
    Adv Immunol. 2001;78:169-232 PMID: 11432204
  13. Regulation of antigen receptor gene assembly in lymphocytes.
    Immunol Res. 2001;23(2-3):121-33 PMID: 11444378
  14. Localized gene-specific induction of accessibility to V(D)J recombination induced by E2A and early B cell factor in nonlymphoid cells.
    J Exp Med. 2001 Sep 3;194(5):645-56 PMID: 11535632
  15. Stepwise activation of the immunoglobulin mu heavy chain gene locus.
    EMBO J. 2001 Nov 15;20(22):6394-403 PMID: 11707410
  16. A change in the structure of Vbeta chromatin associated with TCR beta allelic exclusion.
    J Immunol. 2002 Mar 1;168(5):2316-24 PMID: 11859121
  17. Developmentally controlled and tissue-specific expression of unrearranged VH gene segments.
    Cell. 1985 Feb;40(2):271-81 PMID: 2578321
  18. Separate elements control DJ and VDJ rearrangement in a transgenic recombination substrate.
    EMBO J. 1990 Jan;9(1):117-25 PMID: 2153073
  19. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination.
    Science. 1990 Jun 22;248(4962):1517-23 PMID: 2360047
  20. Virus-transformed pre-B cells show ordered activation but not inactivation of immunoglobulin gene rearrangement and transcription.
    J Exp Med. 1991 Mar 1;173(3):711-20 PMID: 1900081
  21. A V(D)J recombinase-inducible B-cell line: role of transcriptional enhancer elements in directing V(D)J recombination.
    Mol Cell Biol. 1993 Oct;13(10):6223-30 PMID: 8413222
  22. A modified tetracycline-regulated system provides autoregulatory, inducible gene expression in cultured cells and transgenic mice.
    Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6522-6 PMID: 7604026
  23. Initiation of V(D)J recombination in vitro obeying the 12/23 rule.
    Nature. 1996 Mar 7;380(6569):85-8 PMID: 8598914
  24. The RAG1 and RAG2 proteins establish the 12/23 rule in V(D)J recombination.
    Cell. 1996 Apr 5;85(1):107-13 PMID: 8620529
  25. Cell type-specific chromatin structure determines the targeting of V(D)J recombinase activity in vitro.
    Cell. 1996 Jun 14;85(6):887-97 PMID: 8681383
  26. A developmental stage-specific promoter directs germline transcription of D beta J beta gene segments in precursor T lymphocytes.
    J Immunol. 1998 Aug 1;161(3):1399-405 PMID: 9686603
  27. Enhancer control of V(D)J recombination at the TCRbeta locus: differential effects on DNA cleavage and joining.
    Genes Dev. 1998 Aug 1;12(15):2305-17 PMID: 9694796
  28. Alteration of nucleosome structure as a mechanism of transcriptional regulation.
    Annu Rev Biochem. 1998;67:545-79 PMID: 9759497
  29. Evidence that immunoglobulin VH-DJ recombination does not require germ line transcription of the recombining variable gene segment.
    Mol Cell Biol. 1998 Nov;18(11):6253-64 PMID: 9774642
  30. Regulation of V(D)J recombination by transcriptional promoters.
    Mol Cell Biol. 1999 Apr;19(4):2773-81 PMID: 10082543
  31. Control of V(D)J recombinational accessibility of the D beta 1 gene segment at the TCR beta locus by a germline promoter.
    Immunity. 1999 Mar;10(3):313-22 PMID: 10204487
  32. An inducible cell model for studies of V(D)J recombinational control.
    J Immunol Methods. 1999 Apr 22;224(1-2):25-9 PMID: 10357203
  33. V(D)J recombination: on the cutting edge.
    Curr Opin Cell Biol. 1999 Jun;11(3):325-9 PMID: 10395566
  34. Chromatin remodeling directly activates V(D)J recombination.
    Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10788-93 PMID: 10485904
  35. Accessibility control of antigen-receptor variable-region gene assembly: role of cis-acting elements.
    Annu Rev Immunol. 1996;14:459-81 PMID: 8717521
  36. Gene-targeted deletion and replacement mutations of the T-cell receptor beta-chain enhancer: the role of enhancer elements in controlling V(D)J recombination accessibility.
    Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7871-6 PMID: 8755569
  37. Eukaryotic transcription: an interlaced network of transcription factors and chromatin-modifying machines.
    Cell. 1998 Feb 6;92(3):307-13 PMID: 9476891
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.182166699
Published
2002-09-17
Epub
2002-00-26
Pages
12309-14
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC129441
Subset
IM
Grants
NIAID NIH HHS · R01 AI049934 · United States
NIGMS NIH HHS · R37 GM041052 · United States
NIAID NIH HHS · AI49934 · United States
NIGMS NIH HHS · R01 GM041052 · United States
NIAID NIH HHS · AI01412 · United States
NIAID NIH HHS · AI37944 · United States
NIGMS NIH HHS · GM41052 · United States
External Links
PubMed source DOI: 10.1073/pnas.182166699 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2