| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; and
Institute for Genetics, University of Cologne, Cologne, Germany
Allelic exclusion is the process wherein lymphocytes express Ag receptors from only one of two possible alleles, and is effected through a feedback inhibition of further rearrangement of the second allele. The feedback signal is thought to cause chromatin changes that block accessibility of the second allele to the recombinase. To identify the putative chromatin changes associated with allelic exclusion, we assayed for DNase I hypersensitivity, DNA methylation, and transcription in 100 kb of the TCR-ß locus. Contrary to current models, we identified chromatin changes indicative of an active and accessible locus associated with the occurrence of allelic exclusion. Of 11 DNase I hypersensitive sites identified, 3 were induced during CD4-CD8- to CD4+CD8+ thymocyte differentiation, and demethylation and increased germline transcription of the locus were evident. We further examined the role of the most prominently induced site near the TCR-ß enhancer (Eß) in allelic exclusion by targeted mutagenesis. Two other sites were also examined in New Zealand White (NZW) mice that have a natural deletion in the TCR-ß locus. TCR-ß gene recombination and allelic exclusion were normal in both mutant mice, negating dominant roles for the three hypersensitive sites in the control of allelic exclusion. The data suggest that alternative cis-regulatory elements, perhaps contained in the Eß enhancer and/or in the upstream Vß region, are involved in the control of TCR-ß allelic exclusion.
This article has been cited by other articles:
|
|
 |
|
  R. E. McMillan and M. L. Sikes Differential Activation of Dual Promoters Alters D{beta}2 Germline Transcription during Thymocyte Development J. Immunol., March 1, 2008; 180(5): 3218 - 3228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Suzuki, L. Wang, M. Senoo, and S. Habu The positional effect of E{beta} on V{beta} genes of TCR{beta} chain in the ordered rearrangement and allelic exclusion Int. Immunol., December 1, 2005; 17(12): 1553 - 1560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Jackson and M. S. Krangel Allele-Specific Regulation of TCR{beta} Variable Gene Segment Chromatin Structure J. Immunol., October 15, 2005; 175(8): 5186 - 5191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jalota, K. Singh, L. Pavithra, R. Kaul-Ghanekar, S. Jameel, and S. Chattopadhyay Tumor Suppressor SMAR1 Activates and Stabilizes p53 through Its Arginine-Serine-rich Motif J. Biol. Chem., April 22, 2005; 280(16): 16019 - 16029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Nie, S. D. Maika, P. W. Tucker, and P. D. Gottlieb A Role for SATB1, a Nuclear Matrix Association Region-Binding Protein, in the Development of CD8SP Thymocytes and Peripheral T Lymphocytes J. Immunol., April 15, 2005; 174(8): 4745 - 4752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kaul-Ghanekar, S. Majumdar, A. Jalota, N. Gulati, N. Dubey, B. Saha, and S. Chattopadhyay Abnormal V(D)J Recombination of T Cell Receptor {beta} Locus in SMAR1 Transgenic Mice J. Biol. Chem., March 11, 2005; 280(10): 9450 - 9459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kaul-Ghanekar, A. Jalota, L. Pavithra, P. Tucker, and S. Chattopadhyay SMAR1 and Cux/CDP modulate chromatin and act as negative regulators of the TCR{beta} enhancer (E{beta}) Nucleic Acids Res., September 15, 2004; 32(16): 4862 - 4875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Ryu, B. B. Haines, H. R. Lee, Y. H. Kang, D. D. Draganov, M. Lee, C. E. Whitehurst, H. J. Hong, and J. Chen The T-Cell Receptor {beta} Variable Gene Promoter Is Required for Efficient V{beta} Rearrangement but Not Allelic Exclusion Mol. Cell. Biol., August 15, 2004; 24(16): 7015 - 7023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Senoo, L. Wang, D. Suzuki, N. Takeda, Y. Shinkai, and S. Habu Increase of TCR V{beta} Accessibility within E{beta} Regulatory Region Influences its Recombination Frequency But Not Allelic Exclusion J. Immunol., July 15, 2003; 171(2): 829 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rampalli, A. Kulkarni, P. Kumar, D. Mogare, S. Galande, D. Mitra, and S. Chattopadhyay Stimulation of Tat-independent transcriptional processivity from the HIV-1 LTR promoter by matrix attachment regions Nucleic Acids Res., June 15, 2003; 31(12): 3248 - 3256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Mathieu, S. Spicuglia, S. Gorbatch, O. Cabaud, C. Fernex, C. Verthuy, W. M. Hempel, A.-O. Hueber, and P. Ferrier Assessing the Role of the T Cell Receptor beta Gene Enhancer in Regulating Coding Joint Formation during V(D)J Recombination J. Biol. Chem., May 9, 2003; 278(20): 18101 - 18109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Tripathi, A. Jackson, and M. S. Krangel A Change in the Structure of V{beta} Chromatin Associated with TCR {beta} Allelic Exclusion J. Immunol., March 1, 2002; 168(5): 2316 - 2324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sieh and J. Chen Distinct Control of the Frequency and Allelic Exclusion of the V{beta} Gene Rearrangement at the TCR{beta} Locus J. Immunol., August 15, 2001; 167(4): 2121 - 2129. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Mathieu, W. M. Hempel, S. Spicuglia, C. Verthuy, and P. Ferrier 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., September 5, 2000; 192(5): 625 - 636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-P. Zhong, J. Carabana, and M. S. Krangel Flanking nuclear matrix attachment regions synergize with the T cell receptor delta enhancer to promote V(D)J recombination PNAS, October 12, 1999; 96(21): 11970 - 11975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Cocea, A. De Smet, M. Saghatchian, S. Fillatreau, L. Ferradini, S. Schurmans, J.-C. Weill, and C.-A. Reynaud A Targeted Deletion of a Region Upstream from the J{kappa} Cluster Impairs {kappa} Chain Rearrangement In Cis in Mice and in the 103/bcl2 Cell Line J. Exp. Med., May 3, 1999; 189(9): 1443 - 1450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Sikes, C. C. Suarez, and E. M. Oltz Regulation of V(D)J Recombination by Transcriptional Promoters Mol. Cell. Biol., April 1, 1999; 19(4): 2773 - 2781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Sakai, A. Bottaro, L. Davidson, B. P. Sleckman, and F. W. Alt Recombination and transcription of the endogenous Ig heavy chain locus is effected by the Ig heavy chain intronic enhancer core region in the absence of the matrix attachment regions PNAS, February 16, 1999; 96(4): 1526 - 1531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chattopadhyay, C. E. Whitehurst, and J. Chen A Nuclear Matrix Attachment Region Upstream of the T Cell Receptor beta Gene Enhancer Binds Cux/CDP and SATB1 and Modulates Enhancer-dependent Reporter Gene Expression but Not Endogenous Gene Expression J. Biol. Chem., November 6, 1998; 273(45): 29838 - 29846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Sikes, R. J. Gomez, J. Song, and E. M. Oltz A Developmental Stage-Specific Promoter Directs Germline Transcription of D{beta}J{beta} Gene Segments in Precursor T Lymphocytes J. Immunol., August 1, 1998; 161(3): 1399 - 1405. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
