This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Garrett, F. E. Articles by Birshtein, B. K. Search for Related Content PubMed PubMed Citation Articles by Garrett, F. E. Articles by Birshtein, B. K.

Chromatin Architecture near a Potential 3' End of the Igh Locus Involves Modular Regulation of Histone Modifications during B-Cell Development and In Vivo Occupancy at CTCF Sites

Department of Cell Biology, Albert Einstein College of Medicine, Bronx,¹ Department of Biological Sciences, Hunter College, and Graduate School of City University of New York, New York, New York,³ Molecular Pathology Section, Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland²

Received 22 September 2004/ Returned for modification 28 October 2004/ Accepted 22 November 2004

The murine Igh locus has a 3' regulatory region (3' RR) containing four enhancers (hs3A, hs1,2, hs3B, and hs4) at DNase I-hypersensitive sites. The 3' RR exerts long-range effects on class switch recombination (CSR) to several isotypes through its control of germ line transcription. By measuring levels of acetylated histones H3 and H4 and of dimethylated H3 (K4) with chromatin immunoprecipitation assays, we found that early in B-cell development, chromatin encompassing the enhancers of the 3' RR began to attain stepwise modifications typical of an open conformation. The hs4 enhancer was associated with active chromatin initially in pro- and pre-B cells and then together with hs3A, hs1,2, and hs3B in B and plasma cells. Histone modifications were similar in resting splenic B cells and in splenic B cells induced by lipopolysaccharide to undergo CSR. From the pro-B-cell stage onward, the 11-kb region immediately downstream of hs4 displayed H3 and H4 modifications indicative of open chromatin. This region contained newly identified DNase I-hypersensitive sites and several CTCF target sites, some of which were occupied in vivo in a developmentally regulated manner. The open chromatin environment of the extended 3' RR in mature B cells was flanked by regions associated with dimethylated K9 of histone H3. Together, these data suggest that 3' RR elements are located within a specific chromatin subdomain that contains CTCF binding sites and developmentally regulated modules.

This article has been cited by other articles:

• Renaud, S., Pugacheva, E. M., Delgado, M. D., Braunschweig, R., Abdullaev, Z., Loukinov, D., Benhattar, J., Lobanenkov, V. (2007). Expression of the CTCF-paralogous cancer-testis gene, brother of the regulator of imprinted sites (BORIS), is regulated by three alternative promoters modulated by CpG methylation and by CTCF and p53 transcription factors. Nucleic Acids Res 35: 7372-7388 [Abstract] [Full Text]  
• Ju, Z., Volpi, S. A., Hassan, R., Martinez, N., Giannini, S. L., Gold, T., Birshtein, B. K. (2007). Evidence for Physical Interaction between the Immunoglobulin Heavy Chain Variable Region and the 3' Regulatory Region. J. Biol. Chem. 282: 35169-35178 [Abstract] [Full Text]  
• Kimura, A. P., Sizova, D., Handwerger, S., Cooke, N. E., Liebhaber, S. A. (2007). Epigenetic Activation of the Human Growth Hormone Gene Cluster during Placental Cytotrophoblast Differentiation. Mol. Cell. Biol. 27: 6555-6568 [Abstract] [Full Text]  
• Gomos-Klein, J., Harrow, F., Alarcon, J., Ortiz, B. D. (2007). CTCF-Independent, but Not CTCF-Dependent, Elements Significantly Contribute to TCR-{alpha} Locus Control Region Activity. J. Immunol. 179: 1088-1095 [Abstract] [Full Text]  
• Zhang, B., Alaie-Petrillo, A., Kon, M., Li, F., Eckhardt, L. A. (2007). Transcription of a Productively Rearranged Ig VDJC{alpha} Does Not Require the Presence of HS4 in the Igh 3' Regulatory Region. J. Immunol. 178: 6297-6306 [Abstract] [Full Text]  
• Fitzpatrick, G. V., Pugacheva, E. M., Shin, J.-Y., Abdullaev, Z., Yang, Y., Khatod, K., Lobanenkov, V. V., Higgins, M. J. (2007). Allele-Specific Binding of CTCF to the Multipartite Imprinting Control Region KvDMR1. Mol. Cell. Biol. 27: 2636-2647 [Abstract] [Full Text]  
• Laurencikiene, J., Tamosiunas, V., Severinson, E. (2007). Regulation of {epsilon} germline transcription and switch region mutations by IgH locus 3' enhancers in transgenic mice. Blood 109: 159-167 [Abstract] [Full Text]  
• Hodawadekar, S., Wei, F., Yu, D., Thomas-Tikhonenko, A., Atchison, M. L. (2006). Epigenetic Histone Modifications Do Not Control Ig{kappa} Locus Contraction and Intranuclear Localization in Cells with Dual B Cell-Macrophage Potential. J. Immunol. 177: 6165-6171 [Abstract] [Full Text]  
• Lim, J.-H., Cho, S.-J., Park, S.-K., Kim, J., Cho, D., Lee, W. J., Kang, C.-J. (2006). Stage-Specific Expression of Two Neighboring Crlz1 and IgJ Genes during B Cell Development Is Regulated by Their Chromatin Accessibility and Histone Acetylation. J. Immunol. 177: 5420-5429 [Abstract] [Full Text]  
• Schweitzer, B. L., Huang, K. J., Kamath, M. B., Emelyanov, A. V., Birshtein, B. K., DeKoter, R. P. (2006). Spi-C Has Opposing Effects to PU.1 on Gene Expression in Progenitor B Cells. J. Immunol. 177: 2195-2207 [Abstract] [Full Text]  
• Chau, C. M., Zhang, X.-Y., McMahon, S. B., Lieberman, P. M. (2006). Regulation of Epstein-Barr Virus Latency Type by the Chromatin Boundary Factor CTCF.. J. Virol. 80: 5723-5732 [Abstract] [Full Text]  
• Pawlitzky, I., Angeles, C. V., Siegel, A. M., Stanton, M. L., Riblet, R., Brodeur, P. H. (2006). Identification of a Candidate Regulatory Element within the 5' Flanking Region of the Mouse Igh Locus Defined by Pro-B Cell-Specific Hypersensitivity Associated with Binding of PU.1, Pax5, and E2A.. J. Immunol. 176: 6839-6851 [Abstract] [Full Text]  
• Vatolin, S., Abdullaev, Z., Pack, S. D., Flanagan, P. T., Custer, M., Loukinov, D. I., Pugacheva, E., Hong, J. A., Morse, H. III, Schrump, D. S., Risinger, J. I., Barrett, J. C., Lobanenkov, V. V. (2005). Conditional Expression of the CTCF-Paralogous Transcriptional Factor BORIS in Normal Cells Results in Demethylation and Derepression of MAGE-A1 and Reactivation of Other Cancer-Testis Genes. Cancer Res. 65: 7751-7762 [Abstract] [Full Text]  
• Hong, J. A., Kang, Y., Abdullaev, Z., Flanagan, P. T., Pack, S. D., Fischette, M. R., Adnani, M. T., Loukinov, D. I., Vatolin, S., Risinger, J. I., Custer, M., Chen, G. A., Zhao, M., Nguyen, D. M., Barrett, J. C., Lobanenkov, V. V., Schrump, D. S. (2005). Reciprocal Binding of CTCF and BORIS to the NY-ESO-1 Promoter Coincides with Derepression of this Cancer-Testis Gene in Lung Cancer Cells. Cancer Res. 65: 7763-7774 [Abstract] [Full Text]  
• Pugacheva, E. M., Tiwari, V. K., Abdullaev, Z., Vostrov, A. A., Flanagan, P. T., Quitschke, W. W., Loukinov, D. I., Ohlsson, R., Lobanenkov, V. V. (2005). Familial cases of point mutations in the XIST promoter reveal a correlation between CTCF binding and pre-emptive choices of X chromosome inactivation. Hum Mol Genet 14: 953-965 [Abstract] [Full Text]