The CD8alpha gene locus is regulated by the Ikaros family of proteins.
Ikaros family members are important regulatory factors in lymphocyte development. Here we show that Ikaros may play an important role in CD4 versus CD8 lineage commitment decisions by demonstrating: (1) that it binds to regulatory elements in the endogenous CD8alpha locus in vivo using thymocyte chromatin immunoprecipitations, (2) that Ikaros suppresses position effect variegation of transgenes driven by CD8 regulatory elements, and (3) that mice with reduced levels of Ikaros and Aiolos show an apparent increase in CD4 populations with immature phenotype, i.e., cells that failed to activate the CD8alpha gene locus. We propose that Ikaros family members function as activators of the CD8alpha gene locus and that their associated activities are critical for appropriate chromatin remodeling transitions during thymocyte differentiation and lineage commitment.
Harker
Nicola
N
Division of Molecular Immunology, National Institute for Medical Research, Medical Research Council, NW7 1AA, London, United Kingdom.
Naito
Taku
T
Cortes
Marta
M
Hostert
Arnd
A
Hirschberg
Sandra
S
Tolaini
Mauro
M
Roderick
Kathleen
K
Georgopoulos
Katia
K
Kioussis
Dimitris
D
D000818:Animals; D016827:CD8 Antigens / Q000235:genetics* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D051740:Ikaros Transcription Factor; D008198:Lymph Nodes / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D005810:Multigene Family; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012045:Regulatory Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*; D016335:Zinc Fingers
D016827:CD8 Antigens; C431698:CD8alpha antigen; D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor