title: Variegated expression of CD8 alpha resulting from in situ deletion of regulatory sequences.
abstract: The developmental and subset-specific expression of the CD8 genes is under the control of a complex array of regulatory elements distributed along the locus and characterized by DNaseI hypersensitivity. Here we describe the phenotype of mice in which hypersensitive sites 1 and 2 (HSS1 and 2) of DNaseI hypersensitive Cluster II (CII), which are located upstream of the CD8 alpha gene, were deleted by targeted homologous recombination of the endogenous locus. Knockout mice exhibit a variegated expression of the CD8 alpha gene, particularly among the immature CD4(+)8(+) TCR(lo) thymocyte population. We propose that HSS Cluster II regulatory elements are essential in ensuring initiation of chromatin remodeling and establishment of an open configuration in all developing thymocytes that undergo the double-negative to double-positive transition. Furthermore, these sequences contribute to the levels of expression of the CD8 alpha gene.
authors.affiliation: National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Garefalaki
authors.forename: Mark
authors.initials: M
authors.lastname: Coles
authors.forename: Sandra
authors.initials: S
authors.lastname: Hirschberg
authors.forename: Georgia
authors.initials: G
authors.lastname: Mavria
authors.forename: Trisha
authors.initials: T
authors.lastname: Norton
authors.forename: Arnd
authors.initials: A
authors.lastname: Hostert
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kioussis
mesh_terms: D000483:Alleles; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003850:Deoxyribonuclease I / Q000737:chemistry; D004742:Enhancer Elements, Genetic; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006720:Homozygote; D016130:Immunophenotyping; D007700:Kinetics; D051379:Mice; D018448:Models, Immunological; D009924:Organ Culture Techniques; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*; D015533:Transcriptional Activation
chemical_list: D016827:CD8 Antigens; C431698:CD8alpha antigen; D003850:Deoxyribonuclease I