Pre-TCR Signaling and CD8 Gene Bivalent Chromatin Resolution during Thymocyte Development
Copyright policy )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.
- Harvard University United States
- National Institute for Medical Research Tanzania (United Republic of)
- Medical Research Council United Kingdom
- Massachusetts General Hospital United States
- National Institute for Medical Research United Kingdom
CD4-Positive T-Lymphocytes, Mice, Knockout, Precursor Cells, T-Lymphoid, CD8 Antigens, Receptors, Antigen, T-Cell, Cell Differentiation, CD8-Positive T-Lymphocytes, Flow Cytometry, Chromatin, Cell Line, Histones, Mice, Inbred C57BL, Ikaros Transcription Factor, Mice, CD4 Antigens, Animals, Deoxyribonuclease I, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Protein Binding, Signal Transduction
CD4-Positive T-Lymphocytes, Mice, Knockout, Precursor Cells, T-Lymphoid, CD8 Antigens, Receptors, Antigen, T-Cell, Cell Differentiation, CD8-Positive T-Lymphocytes, Flow Cytometry, Chromatin, Cell Line, Histones, Mice, Inbred C57BL, Ikaros Transcription Factor, Mice, CD4 Antigens, Animals, Deoxyribonuclease I, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Protein Binding, Signal Transduction
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