Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 21 January 2000:
Vol. 287. no. 5452, pp. 495 - 498
DOI: 10.1126/science.287.5452.495

Reports

A Role for Histone Acetylation in the Developmental Regulation of V(D)J Recombination

Michelle Taylor McMurry, Michael S. Krangel *

V(D)J recombination is developmentally regulated in vivo by enhancer-dependent changes in the accessibility of chromosomal recombination signal sequences to the recombinase, but the molecular nature of these changes is unknown. Here histone H3 acetylation was measured along versions of a transgenic V(D)J recombination reporter and the endogenous T cell receptor alpha /delta locus. Enhancer activity was shown to impart long-range, developmentally regulated changes in H3 acetylation, and H3 acetylation status was tightly linked to V(D)J recombination. H3 hyperacetylation is proposed as a molecular mechanism coupling enhancer activity to accessibility for V(D)J recombination.

Department of Immunology, Post Office Box 3010, Duke University Medical Center, Durham NC 27710, USA.
*   To whom correspondence should be addressed. E-mail: krang001{at}mc.duke.edu


Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Epigenetic Profile of Ig Genes Is Dynamically Regulated during B Cell Differentiation and Is Modulated by Pre-B Cell Receptor Signaling.
C.-R. Xu and A. J. Feeney (2009)
J. Immunol. 182, 1362-1369
   Abstract »    Full Text »    PDF »
Functional Analysis of Histone Methyltransferase G9a in B and T Lymphocytes.
L. R. Thomas, H. Miyashita, R. M. Cobb, S. Pierce, M. Tachibana, E. Hobeika, M. Reth, Y. Shinkai, and E. M. Oltz (2008)
J. Immunol. 181, 485-493
   Abstract »    Full Text »    PDF »
Modulation of immunoglobulin gene conversion frequency and distribution by the histone deacetylase HDAC2 in chicken DT40..
W. Lin, S.-i. Hashimoto, H. Seo, T. Shibata, and K. Ohta (2008)
Genes Cells 13, 255-268
   Abstract »    Full Text »    PDF »
Productive Coupling of Accessible V{beta}14 Segments and DJ{beta} Complexes Determines the Frequency of V{beta}14 Rearrangement.
S. Ranganath, A. C. Carpenter, M. Gleason, A. C. Shaw, C. H. Bassing, and F. W. Alt (2008)
J. Immunol. 180, 2339-2346
   Abstract »    Full Text »    PDF »
Dynamic Changes in Accessibility, Nuclear Positioning, Recombination, and Transcription at the Ig{kappa} Locus.
S. P. Fitzsimmons, R. M. Bernstein, E. E. Max, J. A. Skok, and M. A. Shapiro (2007)
J. Immunol. 179, 5264-5273
   Abstract »    Full Text »    PDF »
Acetylation increases access of remodelling complexes to their nucleosome targets to enhance initiation of V(D)J recombination.
K. P. Nightingale, M. Baumann, A. Eberharter, A. Mamais, P. B. Becker, and J. Boyes (2007)
Nucleic Acids Res. 35, 6311-6321
   Abstract »    Full Text »    PDF »
Replication Fork Stalling at Natural Impediments.
E. V. Mirkin and S. M. Mirkin (2007)
Microbiol. Mol. Biol. Rev. 71, 13-35
   Abstract »    Full Text »    PDF »
Role for rearranged variable gene segments in directing secondary T cell receptor {alpha} recombination.
A. Hawwari and M. S. Krangel (2007)
PNAS 104, 903-907
   Abstract »    Full Text »    PDF »
Genome-wide prediction of conserved and nonconserved enhancers by histone acetylation patterns.
T.-y. Roh, G. Wei, C. M. Farrell, and K. Zhao (2007)
Genome Res. 17, 74-81
   Abstract »    Full Text »    PDF »
Critical roles of the immunoglobulin intronic enhancers in maintaining the sequential rearrangement of IgH and Igk loci.
M. A. Inlay, T. Lin, H. H. Gao, and Y. Xu (2006)
J. Exp. Med. 203, 1721-1732
   Abstract »    Full Text »    PDF »
A Role for MAPK in Feedback Inhibition of Tcrb Recombination..
A. M. Jackson and M. S. Krangel (2006)
J. Immunol. 176, 6824-6830
   Abstract »    Full Text »    PDF »
Expression of TCR{alpha}beta Partly Rescues Developmental Arrest and Apoptosis of {alpha}beta T cells in Bcl11b-/- Mice.
J. Inoue, T. Kanefuji, K. Okazuka, H. Watanabe, Y. Mishima, and R. Kominami (2006)
J. Immunol. 176, 5871-5879
   Abstract »    Full Text »    PDF »
Activation of V(D)J Recombination at the IgH Chain JH Locus Occurs within a 6-Kilobase Chromatin Domain and Is Associated with Nucleosomal Remodeling.
J. Maes, S. Chappaz, P. Cavelier, L. O'Neill, B. Turner, F. Rougeon, and M. Goodhardt (2006)
J. Immunol. 176, 5409-5417
   Abstract »    Full Text »    PDF »
E2A and IRF-4/Pip Promote Chromatin Modification and Transcription of the Immunoglobulin {kappa} Locus in Pre-B Cells.
A. S. Lazorchak, M. S. Schlissel, and Y. Zhuang (2006)
Mol. Cell. Biol. 26, 810-821
   Abstract »    Full Text »    PDF »
AID-dependent histone acetylation is detected in immunoglobulin S regions.
L. Wang, N. Whang, R. Wuerffel, and A. L. Kenter (2006)
J. Exp. Med. 203, 215-226
   Abstract »    Full Text »    PDF »
The Extent of Histone Acetylation Correlates with the Differential Rearrangement Frequency of Individual VH Genes in Pro-B Cells.
C. R. Espinoza and A. J. Feeney (2005)
J. Immunol. 175, 6668-6675
   Abstract »    Full Text »    PDF »
Allele-Specific Regulation of TCR{beta} Variable Gene Segment Chromatin Structure.
A. M. Jackson and M. S. Krangel (2005)
J. Immunol. 175, 5186-5191
   Abstract »    Full Text »    PDF »
Regulation of TCR {delta} and {alpha} repertoires by local and long-distance control of variable gene segment chromatin structure.
A. Hawwari and M. S. Krangel (2005)
J. Exp. Med. 202, 467-472
   Abstract »    Full Text »    PDF »
Developmental Activation of the TCR {alpha} Enhancer Requires Functional Collaboration among Proteins Bound Inside and Outside the Core Enhancer.
N. Balmelle, N. Zamarreno, M. S. Krangel, and C. Hernandez-Munain (2004)
J. Immunol. 173, 5054-5063
   Abstract »    Full Text »    PDF »
ATP-dependent Remodeling by SWI/SNF and ISWI Proteins Stimulates V(D)J Cleavage of 5 S Arrays.
N. Patenge, S. K. Elkin, and M. A. Oettinger (2004)
J. Biol. Chem. 279, 35360-35367
   Abstract »    Full Text »    PDF »
Loss of CARM1 Results in Hypomethylation of Thymocyte Cyclic AMP-regulated Phosphoprotein and Deregulated Early T Cell Development.
J. Kim, J. Lee, N. Yadav, Q. Wu, C. Carter, S. Richard, E. Richie, and M. T. Bedford (2004)
J. Biol. Chem. 279, 25339-25344
   Abstract »    Full Text »    PDF »
Pax5 Activates Immunoglobulin Heavy Chain V to DJ Rearrangement in Transgenic Thymocytes.
L.-Y. Hsu, H.-E. Liang, K. Johnson, C. Kang, and M. S. Schlissel (2004)
J. Exp. Med. 199, 825-830
   Abstract »    Full Text »    PDF »
Developmental Separation of V(D)J Recombinase Expression and Initiation of IgH Recombination in B Lineage Progenitors In Vivo.
L. Borghesi and R. M. Gerstein (2004)
J. Exp. Med. 199, 483-489
   Abstract »    Full Text »    PDF »
Transcription-Coupled Events Associating with Immunoglobulin Switch Region Chromatin.
Y. Nambu, M. Sugai, H. Gonda, C.-G. Lee, T. Katakai, Y. Agata, Y. Yokota, and A. Shimizu (2003)
Science 302, 2137-2140
   Abstract »    Full Text »    PDF »
Transcriptional Regulation of ILT Family Receptors.
H. Nakajima, A. Asai, A. Okada, L. Ping, F. Hamajima, T. Sata, and K. Isobe (2003)
J. Immunol. 171, 6611-6620
   Abstract »    Full Text »    PDF »
Antigen receptor loci poised for V(D)J rearrangement are broadly associated with BRG1 and flanked by peaks of histone H3 dimethylated at lysine 4.
K. B. Morshead, D. N. Ciccone, S. D. Taverna, C. D. Allis, and M. A. Oettinger (2003)
PNAS 100, 11577-11582
   Abstract »    Full Text »    PDF »
A Novel Arabidopsis Acetyltransferase Interacts with the Geminivirus Movement Protein NSP.
R. C. McGarry, Y. D. Barron, M. F. Carvalho, J. E. Hill, D. Gold, E. Cheung, W. L. Kraus, and S. G. Lazarowitz (2003)
PLANT CELL 15, 1605-1618
   Abstract »    Full Text »    PDF »
Changes in Histone Acetylation Are Associated with Differences in Accessibility of VH Gene Segments to V-DJ Recombination during B-Cell Ontogeny and Development.
K. Johnson, C. Angelin-Duclos, S. Park, and K. L. Calame (2003)
Mol. Cell. Biol. 23, 2438-2450
   Abstract »    Full Text »    PDF »
T cell receptor (TCR) alpha /delta locus enhancer identity and position are critical for the assembly of TCR delta and alpha variable region genes.
C. H. Bassing, R. E. Tillman, B. B. Woodman, D. Canty, R. J. Monroe, B. P. Sleckman, and F. W. Alt (2003)
PNAS 100, 2598-2603
   Abstract »    Full Text »    PDF »
Accessibility control and machinery of immunoglobulin class switch recombination.
K. Zhang (2003)
J. Leukoc. Biol. 73, 323-332
   Abstract »    Full Text »    PDF »
Distinct Roles for c-Myb and Core Binding Factor/Polyoma Enhancer-Binding Protein 2 in the Assembly and Function of a Multiprotein Complex on the TCR {delta} Enhancer In Vivo.
C. Hernandez-Munain and M. S. Krangel (2002)
J. Immunol. 169, 4362-4369
   Abstract »    Full Text »    PDF »
Regulation of V(D)J recombination: A dominant role for promoter positioning in gene segment accessibility.
M. L. Sikes, A. Meade, R. Tripathi, M. S. Krangel, and E. M. Oltz (2002)
PNAS 99, 12309-12314
   Abstract »    Full Text »    PDF »
High Frequency of Matrix Attachment Regions and Cut-Like Protein x/CCAAT-Displacement Protein and B Cell Regulator of IgH Transcription Binding Sites Flanking Ig V Region Genes.
P. Goebel, A. Montalbano, N. Ayers, E. Kompfner, L. Dickinson, C. F. Webb, and A. J. Feeney (2002)
J. Immunol. 169, 2477-2487
   Abstract »    Full Text »    PDF »
Replication and Subnuclear Location Dynamics of the Immunoglobulin Heavy-Chain Locus in B-Lineage Cells.
J. Zhou, O. V. Ermakova, R. Riblet, B. K. Birshtein, and C. L. Schildkraut (2002)
Mol. Cell. Biol. 22, 4876-4889
   Abstract »    Full Text »    PDF »
Control of IL-2R{alpha} gene expression: structural changes within the proximal enhancer/core promoter during T-cell development.
J.-H. Yeh, S. Spicuglia, S. Kumar, A. Sanchez-Sevilla, P. Ferrier, and J. Imbert (2002)
Nucleic Acids Res. 30, 1944-1951
   Abstract »    Full Text »    PDF »
Subnuclear Compartmentalization of Immunoglobulin Loci During Lymphocyte Development.
S. T. Kosak, J. A. Skok, K. L. Medina, R. Riblet, M. M. Le Beau, A. G. Fisher, and H. Singh (2002)
Science 296, 158-162
   Abstract »    Full Text »    PDF »
Role of Histone Deacetylation in Developmentally Programmed DNA Rearrangements in Tetrahymena thermophila.
S. Duharcourt and M.-C. Yao (2002)
Eukaryot. Cell 1, 293-303
   Abstract »    Full Text »    PDF »
The Ubiquitously Expressed DNA-Binding Protein Late SV40 Factor Binds Ig Switch Regions and Represses Class Switching to IgA.
E. E. Drouin, C. E. Schrader, J. Stavnezer, and U. Hansen (2002)
J. Immunol. 168, 2847-2856
   Abstract »    Full Text »    PDF »
A Change in the Structure of V{beta} Chromatin Associated with TCR {beta} Allelic Exclusion.
R. Tripathi, A. Jackson, and M. S. Krangel (2002)
J. Immunol. 168, 2316-2324
   Abstract »    Full Text »    PDF »
Early Growth Response Transcription Factors Are Required for Development of CD4-CD8- Thymocytes to the CD4+CD8+ Stage.
M. Carleton, M. C. Haks, S. A. A. Smeele, A. Jones, S. M. Belkowski, M. A. Berger, P. Linsley, A. M. Kruisbeek, and D. L. Wiest (2002)
J. Immunol. 168, 1649-1658
   Abstract »    Full Text »    PDF »
The Cleavage Efficiency of the Human Immunoglobulin Heavy Chain VH Elements by the RAG Complex. IMPLICATIONS FOR THE IMMUNE REPERTOIRE.
K. Yu, A. Taghva, and M. R. Lieber (2002)
J. Biol. Chem. 277, 5040-5046
   Abstract »    Full Text »    PDF »
The Histone Deacetylase Inhibitor Sodium Butyrate Induces DNA Topoisomerase II{alpha} Expression and Confers Hypersensitivity to Etoposide in Human Leukemic Cell Lines.
E. U. Kurz, S. E. Wilson, K. B. Leader, B. P. Sampey, W. P. Allan, J. C. Yalowich, and D. J. Kroll (2001)
Mol. Cancer Ther. 1, 121-131
   Abstract »    Full Text »    PDF »
Cutting Edge: Histone Acetylation and Recombination at the TCR{gamma} Locus Follows IL-7 Induction.
J. Huang, S. K. Durum, and K. Muegge (2001)
J. Immunol. 167, 6073-6077
   Abstract »    Full Text »    PDF »
Limited effect of chromatin remodeling on D{beta}-to-J{beta} recombination in CD4+CD8+ thymocyte: implications for a new aspect in the regulation of TCR {beta} gene recombination.
M. Senoo, N. Mochida, L. Wang, Y. Matsumura, D. Suzuki, N. Takeda, Y. Shinkai, and S. Habu (2001)
Int. Immunol. 13, 1405-1414
   Abstract »    Full Text »    PDF »
The murine beta -globin locus control region regulates the rate of transcription but not the hyperacetylation of histones at the active genes.
D. Schubeler, M. Groudine, and M. A. Bender (2001)
PNAS
   Abstract »    Full Text »    PDF »
Localized Gene-specific Induction of Accessibility to V(D)J Recombination Induced by E2A and Early B Cell Factor in Nonlymphoid Cells.
P. Goebel, N. Janney, J. R. Valenzuela, W. J. Romanow, C. Murre, and A. J. Feeney (2001)
J. Exp. Med. 194, 645-656
   Abstract »    Full Text »    PDF »
Histone Deacetylase 4 Possesses Intrinsic Nuclear Import and Export Signals.
A. H. Wang and X.-J. Yang (2001)
Mol. Cell. Biol. 21, 5992-6005
   Abstract »    Full Text »    PDF »
The Role of Recombination Activating Gene (RAG) Reinduction in Thymocyte Development In Vivo.
N. Yannoutsos, P. Wilson, W. Yu, H. T. Chen, A. Nussenzweig, H. Petrie, and M. C. Nussenzweig (2001)
J. Exp. Med. 194, 471-480
   Abstract »    Full Text »    PDF »
Distinct Control of the Frequency and Allelic Exclusion of the V{beta} Gene Rearrangement at the TCR{beta} Locus.
P. Sieh and J. Chen (2001)
J. Immunol. 167, 2121-2129
   Abstract »    Full Text »    PDF »
Both TCR{alpha} and TCR{delta} Chain Diversity Are Regulated During Thymic Ontogeny.
M. Gallagher, P. Obeid, P. N. Marche, and E. Jouvin-Marche (2001)
J. Immunol. 167, 1447-1453
   Abstract »    Full Text »    PDF »
Chromatin Remodeling at the Ig Loci Prior to V(D)J Recombination.
J. Maes, L. P. O'Neill, P. Cavelier, B. M. Turner, F. Rougeon, and M. Goodhardt (2001)
J. Immunol. 167, 866-874
   Abstract »    Full Text »    PDF »
Transcription Factor NF-{{kappa}}B Regulates Ig{{lambda}} Light Chain Gene Rearrangement.
H. H. Bendall, M. L. Sikes, and E. M. Oltz (2001)
J. Immunol. 167, 264-269
   Abstract »    Full Text »    PDF »
Induction of Germline Transcription in the Human TCR{{gamma}} Locus by STAT5.
H.-C. Lee, S.-K. Ye, T. Honjo, and K. Ikuta (2001)
J. Immunol. 167, 320-326
   Abstract »    Full Text »    PDF »
Control of chromatin accessibility for V(D)J recombination by interleukin-7.
J. Huang and K. Muegge (2001)
J. Leukoc. Biol. 69, 907-911
   Abstract »    Full Text »    PDF »
Nongenic, bidirectional transcription precedes and may promote developmental DNA deletion in Tetrahymena thermophila.
D. L. Chalker and M.-C. Yao (2001)
Genes & Dev. 15, 1287-1298
   Abstract »    Full Text »
Increased Transcription Levels Induce Higher Mutation Rates in a Hypermutating Cell Line.
J. Bachl, C. Carlson, V. Gray-Schopfer, M. Dessing, and C. Olsson (2001)
J. Immunol. 166, 5051-5057
   Abstract »    Full Text »    PDF »
Histone Acetylation Determines the Developmentally Regulated Accessibility for T Cell Receptor {{gamma}} Gene Recombination.
Y. Agata, T. Katakai, S.-K. Ye, M. Sugai, H. Gonda, T. Honjo, K. Ikuta, and A. Shimizu (2001)
J. Exp. Med. 193, 873-880
   Abstract »    Full Text »    PDF »
V(D)J Recombination Becomes Accessible.
M. S. Krangel (2001)
J. Exp. Med. 193, F27-F30
   Full Text »    PDF »
NF-{{kappa}}B p50-Dependent In Vivo Footprints at Ig S{{gamma}}3 DNA Are Correlated with {micro}{->}{{gamma}}3 Switch Recombination.
R. A. Wuerffel, L. Ma, and A. L. Kenter (2001)
J. Immunol. 166, 4552-4559
   Abstract »    Full Text »    PDF »
Induction of a Diverse T Cell Receptor {{gamma}}/{{delta}} Repertoire by the Helix-Loop-Helix Proteins E2A and HEB in Nonlymphoid Cells.
J. K. Ghosh, W. J. Romanow, and C. Murre (2001)
J. Exp. Med. 193, 769-776
   Abstract »    Full Text »    PDF »
Insertion of Phosphoglycerine Kinase (PGK)-Neo 5' of J{{lambda}}1 Dramatically Enhances VJ{{lambda}}1 Rearrangement.
T. Sun and U. Storb (2001)
J. Exp. Med. 193, 699-712
   Abstract »    Full Text »    PDF »
Matrix Attachment Region-Dependent Function of the Immunoglobulin {micro} Enhancer Involves Histone Acetylation at a Distance without Changes in Enhancer Occupancy.
L. A. Fernández, M. Winkler, and R. Grosschedl (2001)
Mol. Cell. Biol. 21, 196-208
   Abstract »    Full Text »
Histone H4 Acetylation of Euchromatin and Heterochromatin Is Cell Cycle Dependent and Correlated with Replication Rather Than with Transcription.
Z. Jasencakova, A. Meister, J. Walter, B. M. Turner, and I. Schubert (2000)
PLANT CELL 12, 2087-2100
   Abstract »    Full Text »
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.
N. Mathieu, W. M. Hempel, S. Spicuglia, C. Verthuy, and P. Ferrier (2000)
J. Exp. Med. 192, 625-636
   Abstract »    Full Text »    PDF »
Acetylation of Histones and Transcription-Related Factors.
D. E. Sterner and S. L. Berger (2000)
Microbiol. Mol. Biol. Rev. 64, 435-459
   Abstract »    Full Text »    PDF »
A Novel Chromodomain Protein, Pdd3p, Associates with Internal Eliminated Sequences during Macronuclear Development in Tetrahymena thermophila.
M. A. Nikiforov, M. A. Gorovsky, and C. D. Allis (2000)
Mol. Cell. Biol. 20, 4128-4134
   Abstract »    Full Text »
Replication Factors MCM2 and ORC1 Interact with the Histone Acetyltransferase HBO1.
T. W. Burke, J. G. Cook, M. Asano, and J. R. Nevins (2001)
J. Biol. Chem. 276, 15397-15408
   Abstract »    Full Text »    PDF »
The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases.
J. Landry, A. Sutton, S. T. Tafrov, R. C. Heller, J. Stebbins, L. Pillus, and R. Sternglanz (2000)
PNAS 97, 5807-5811
   Abstract »    Full Text »    PDF »
The murine beta -globin locus control region regulates the rate of transcription but not the hyperacetylation of histones at the active genes.
D. Schubeler, M. Groudine, and M. A. Bender (2001)
PNAS 98, 11432-11437
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)