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Publication : Evidence for distinct CD4 silencer functions at different stages of thymocyte differentiation.

First Author  Taniuchi I Year  2002
Journal  Mol Cell Volume  10
Issue  5 Pages  1083-96
PubMed ID  12453416 Mgi Jnum  J:80576
Mgi Id  MGI:2446370 Doi  10.1016/s1097-2765(02)00735-9
Citation  Taniuchi I, et al. (2002) Evidence for distinct CD4 silencer functions at different stages of thymocyte differentiation. Mol Cell 10(5):1083-96
abstractText  An intronic silencer within the CD4 gene is the critical cis regulatory element for T cell subset-specific expression of CD4. We have combined transfection studies with gene targeting in mice to identify several key sequences within the silencer core that are required for gene silencing during thymocyte development. In mice, mutations in individual sites resulted in variegated, but heritable, derepression of CD4 in mature CD8(+) T lymphocytes, whereas compound mutations resulted in full derepression. These results indicate that there is partial redundancy in recruiting a chromatin remodeling machinery that results in epigenetic silencing. Mutations in single sites also resulted in partial derepression of CD4 in immature double-negative thymocytes, but there was no apparent variegation. These findings suggest two distinct modes of CD4 silencer function at different developmental stages: active repression in CD4(-)CD8(-) thymocytes, in which silencing must be reversible, and epigenetic gene silencing upon differentiation to the CD8(+) cytotoxic T cell lineage.
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