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Publication : Pre-TCR signaling and CD8 gene bivalent chromatin resolution during thymocyte development.

First Author  Harker N Year  2011
Journal  J Immunol Volume  186
Issue  11 Pages  6368-77
PubMed ID  21515796 Mgi Jnum  J:173200
Mgi Id  MGI:5013532 Doi  10.4049/jimmunol.1003567
Citation  Harker N, et al. (2011) Pre-TCR Signaling and CD8 Gene Bivalent Chromatin Resolution during Thymocyte Development. J Immunol 186(11):6368-77
abstractText  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 1alpha on the locus during these processes may participate in the complex regulation of CD8.
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