Regulation of TCR δ and α repertoires by local and long-distance control of variable gene segment chromatin structure

作者: Abbas Hawwari , Michael S. Krangel

DOI: 10.1084/JEM.20050680

关键词:

摘要: Murine Tcrd and Tcra gene segments reside in a single genetic locus undergo recombination CD4 − CD8 (double negative [DN]) + positive [DP]) thymocytes, respectively. TcraTcrd variable are subject to complex regulation. Only small subset of ∼100 contributes substantially the adult TCR δ repertoire. Moreover, although most contribute α repertoire, that J proximal preferentially used during primary recombination. We investigate role local chromatin accessibility determining developmental pattern segment find be heterogeneous with respect acetylation histones H3 H4. Those dominate repertoire hyperacetylated DN independent their position locus. show dramatic increases histone germline transcription DP result super long-distance regulation by enhancer. Our results imply differences biases thymocytes extend distance over which enhancer can regulate structure remarkable 525 kb.

参考文章(30)
Michael S. Krangel, Xiao-Ping Zhong, Enhancer-blocking activity within the DNase I hypersensitive site 2 to 6 region between the TCR alpha and Dad1 genes. Journal of Immunology. ,vol. 163, pp. 295- 300 ,(1999)
Abbas Hawwari, Cheryl Bock, Michael S Krangel, Regulation of T cell receptor alpha gene assembly by a complex hierarchy of germline Jalpha promoters. Nature Immunology. ,vol. 6, pp. 481- 489 ,(2005) , 10.1038/NI1189
Julia Weber-Arden, Oliver M. Wilbert, Dieter Kabelitz, Bernhard Arden, Vδ Repertoire During Thymic Ontogeny Suggests Three Novel Waves of γδ TCR Expression The Journal of Immunology. ,vol. 164, pp. 1002- 1012 ,(2000) , 10.4049/JIMMUNOL.164.2.1002
Maighréad Gallagher, Patricia Obeïd, Patrice N. Marche, Evelyne Jouvin-Marche, Both TCRα and TCRδ Chain Diversity Are Regulated During Thymic Ontogeny Journal of Immunology. ,vol. 167, pp. 1447- 1453 ,(2001) , 10.4049/JIMMUNOL.167.3.1447
Catherine Aude-Garcia, Evelyne Jouvin-Marche, Maighr�ad Gallagher, Patrice N. Marche, Preferential ADV-AJ association during recombination in the mouse T-cell receptor alpha/delta locus. Immunogenetics. ,vol. 52, pp. 224- 230 ,(2001) , 10.1007/S002510000266
Robert J Monroe, Barry P Sleckman, Brianna C Monroe, Bernard Khor, Steven Claypool, Roger Ferrini, Laurie Davidson, Frederick W Alt, Developmental Regulation of TCRδ Locus Accessibility and Expression by the TCRδ Enhancer Immunity. ,vol. 10, pp. 503- 513 ,(1999) , 10.1016/S1074-7613(00)80050-3
Pablo Pereira, Véronique Hermitte, Marie-Pierre Lembezat, Laurent Boucontet, Véronique Azuara, Kalliopi Grigoriadou, Developmentally regulated and lineage‐specific rearrangement of T cell receptor Vα/δ gene segments European Journal of Immunology. ,vol. 30, pp. 1988- 1997 ,(2000) , 10.1002/1521-4141(200007)30:7<1988::AID-IMMU1988>3.0.CO;2-W
Bernhard Arden, StephenP. Clark, Dieter Kabelitz, TakW. Mak, Mouse T-cell receptor variable gene segment families. Immunogenetics. ,vol. 42, pp. 455- 500 ,(1995) , 10.1007/BF00172176
Martin Fuxa, Jane Skok, Abdallah Souabni, Giorgia Salvagiotto, Esther Roldan, Meinrad Busslinger, Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene Genes & Development. ,vol. 18, pp. 411- 422 ,(2004) , 10.1101/GAD.291504