During B cell and T cell development, the lymphoid-specific proteins RAG-1 and RAG-2 act together to initiate the assembly of antigen receptor genes through a series of site-specific somatic DNA rearrangements that are collectively called variable-diversity-joining (V(D)J) recombination. In the past 20 years, a great deal has been learned about the enzymatic activities of the RAG-1-RAG-2 complex. Recent studies have identified several new and exciting regulatory functions of the RAG-1-RAG-2 complex. Here we discuss some of these functions and suggest that the RAG-1-RAG-2 complex nucleates a specialized subnuclear compartment that we call the 'V(D)J recombination factory'.
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http://dx.doi.org/10.1038/ni.1776 | DOI Listing |
Zootaxa
October 2015
Museum of Zoology, Senckenberg Dresden, A. B. Meyer Building, D-01109 Dresden, Germany.
We examined differentiation within the Colombian wood turtle Rhinoclemmys melanosterna, and among R. melanosterna and the closely allied species R. diademata, R.
View Article and Find Full Text PDFJ Immunol
September 2011
Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada.
Miz-1 is a Broad-complex, Tramtrack and Bric-à-brac/pox virus zinc finger domain (BTB/POZ)-containing protein expressed in lymphoid precursors that can activate or repress transcription. We report in this article that mice expressing a nonfunctional Miz-1 protein lacking the BTB/POZ domain (Miz-1(ΔPOZ)) have a severe differentiation block at the pre-T cell "β-selection" checkpoint, evident by a drastic reduction of CD4(-)CD8(-) double-negative-3 (DN3) and DN4 cell numbers. T cell-specific genes including Rag-1, Rag-2, CD3ε, pTα, and TCRβ are expressed in Miz-1-deficient cells and V(D)J recombination is intact, but few DN3/DN4 cells express a surface pre-TCR.
View Article and Find Full Text PDFNat Immunol
August 2009
Howard Hughes Medical Institute, Department of Biology, Cambridge, Massachusetts, USA.
During B cell and T cell development, the lymphoid-specific proteins RAG-1 and RAG-2 act together to initiate the assembly of antigen receptor genes through a series of site-specific somatic DNA rearrangements that are collectively called variable-diversity-joining (V(D)J) recombination. In the past 20 years, a great deal has been learned about the enzymatic activities of the RAG-1-RAG-2 complex. Recent studies have identified several new and exciting regulatory functions of the RAG-1-RAG-2 complex.
View Article and Find Full Text PDFJ Immunol
February 2006
Department of Microbiology/Immunology, Vanderbilt University Medical School, Nashville, TN 37232, USA.
The assembly of Ag receptor genes by V(D)J recombination is regulated by transcriptional promoters and enhancers which control chromatin accessibility at Ig and TCR gene segments to the RAG-1/RAG-2 recombinase complex. Paradoxically, germline deletions of the IgH enhancer (Emu) only modestly reduce D(H)-->J(H) rearrangements when assessed in peripheral B cells. However, deletion of Emu severely impairs recombination of V(H) gene segments, which are located over 100 kb away.
View Article and Find Full Text PDFMol Cell Biochem
October 2003
Grupo de Imunogenética Molecular, Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, Brasil.
The V(D)J recombination of TCRalpha and beta in early developing T-cells is a highly modulated phenomenon initiated and completed by recombinase complex (RAG-1 and RAG-2), and regulated by other gene products such as interleukins. To further evaluate the association of several other gene products with the evolution of TCRVbeta8.1 V(D)J rearrangements in vivo, the mRNA expression levels of seven interleukins, three cytokines, receptors TCRVbeta8.
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