title: Ikaros promotes rearrangement of TCR α genes in an Ikaros null thymoma cell line.
abstract: Ikaros is important in the development and maintenance of the lymphoid system, functioning in part by associating with chromatin-remodeling complexes. We have studied the functions of Ikaros in the transition from pre-T cell to the CD4(+) CD8(+)  thymocyte using an Ikaros null CD4(-) CD8(-)  mouse thymoma cell line (JE131). We demonstrate that this cell line carries a single functional TCR β gene rearrangement and expresses a surface pre-TCR. JE131 cells also carry nonfunctional rearrangements on both alleles of their TCR α loci. Retroviral reintroduction of Ikaros dramatically increased the rate of transcription in the α locus and TCR Vα/Jα recombination resulting in the appearance of many new αβTCR(+)  cells. The process is RAG dependent, requires switch/sucrose nonfermentable chromatin-remodeling complexes and is coincident with the binding of Ikaros to the TCR α enhancer. Furthermore, knockdown of Mi2/nucleosome remodeling and deacetylase complexes increased the frequency of TCR α rearrangement. Our data suggest that Ikaros controls Vα/Jα recombination in T cells by controlling access of the transcription and recombination machinery to the TCR α loci. The JE131 cell line should prove to be a very useful tool for studying the molecular details of this and other processes involved in the pre-T cell to αβTCR(+)  CD4(+) CD8(+)  thymocyte transition.
authors.affiliation: Howard Hughes Medical Institute, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Collins
authors.forename: Eric T
authors.initials: ET
authors.lastname: Clambey
authors.forename: James
authors.initials: J
authors.lastname: Scott-Browne
authors.forename: Janice
authors.initials: J
authors.lastname: White
authors.forename: Philippa
authors.initials: P
authors.lastname: Marrack
authors.forename: James
authors.initials: J
authors.lastname: Hagman
authors.forename: John W
authors.initials: JW
authors.lastname: Kappler
mesh_terms: D000483:Alleles; D000818:Animals; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051740:Ikaros Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D008215:Lymphocytes, Null / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000378:metabolism; D013945:Thymoma / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; C064658:RAG-1 protein; D051740:Ikaros Transcription Factor; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex