title: Pre-TCR signaling and CD8 gene bivalent chromatin resolution during thymocyte development.
abstract: The CD8 gene is silent in CD4(-)CD8(-) double-negative thymocytes, expressed in CD4(+)CD8(+) double-positive cells, and silenced in cells committing to the CD4(+) single-positive (SP) lineage, remaining active in the CD8(+) SP lineage. In this study, we show that the chromatin of the CD8 locus is remodeled in C57BL/6 and B6/J Rag1(-/-) MOM double-negative thymocytes as indicated by DNaseI hypersensitivity and widespread bivalent chromatin marks. Pre-TCR signaling coincides with chromatin bivalency resolution into monovalent activating modifications in double-positive and CD8 SP cells. Shortly after commitment to CD4 SP cell lineage, monovalent repressive characteristics and chromatin inaccessibility are established. Differential binding of Ikaros, NuRD, and heterochromatin protein 1α on the locus during these processes may participate in the complex regulation of CD8.
authors.affiliation: Division of Molecular Immunology, National Institute for Medical Research, Medical Research Council, London NW7 1AA, United Kingdom. nharker@nimr.mrc.ac.uk
authors.forename: Nicola
authors.initials: N
authors.lastname: Harker
authors.forename: Anna
authors.initials: A
authors.lastname: Garefalaki
authors.forename: Ursula
authors.initials: U
authors.lastname: Menzel
authors.forename: Eleni
authors.initials: E
authors.lastname: Ktistaki
authors.forename: Taku
authors.initials: T
authors.lastname: Naito
authors.forename: Katia
authors.initials: K
authors.lastname: Georgopoulos
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kioussis
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D005434:Flow Cytometry; D006657:Histones / Q000378:metabolism; D051740:Ikaros Transcription Factor / Q000378:metabolism; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D002843:Chromatin; D006657:Histones; D011948:Receptors, Antigen, T-Cell; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor; D003850:Deoxyribonuclease I; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex