Nucleoprotein structure of the CD4 locus: Implications for the mechanisms underlying CD4 regulation during T cell development

@article{citeulike:2520243, abstract = {The CD4 gene is regulated in a stage-specific manner during T cell development, being repressed in CD4CD8 double-negative (DN) and CD8 cells, but expressed in CD4+CD8+ double-positive (DP) and CD4 cells. Furthermore, the expression/repression pattern is reversible in developing (DN and DP) thymocytes, but irreversible in mature (CD4 and CD8) T cells. Here, we explored the molecular mechanisms underlying this complex mode of regulation by examining the nucleoprotein structure of the CD4 locus throughout T cell development and in DN cells lacking the CD4 silencer. In DN cells, the CD4 enhancer is preloaded with multiple transcription activators, but p300 recruitment is impaired by the silencer that is associated with the repressor Runx1. DP cells achieve high-level CD4 expression via a combination of CD4 derepression and true activation, but Runx1 remains bound to the silencer that retains an open chromatin configuration. In CD4 cells, Runx1 dissociates from the silencer that has become less accessible, and CD4 transcription appears to be achieved via a mechanism distinct from that operating in DP cells. In CD8 cells, the CD4 promoter becomes incorporated into heterochromatin-like structure. Our data shed light on the molecular basis of CD4 regulation and provide a conceptual framework for understanding how the same regulatory elements can mediate both reversible and irreversible CD4 regulation. 10.1073/pnas.0800810105}, author = {Yu, Ming and Wan, Mimi and Zhang, Jianmin and Wu, Jie and Khatri, Rohini and Chi, Tian }, citeulike-article-id = {2520243}, doi = {10.1073/pnas.0800810105}, journal = {Proceedings of the National Academy of Sciences}, month = {March}, number = {10}, pages = {3873--3878}, posted-at = {2008-03-12 13:21:37}, priority = {2}, title = {Nucleoprotein structure of the CD4 locus: Implications for the mechanisms underlying CD4 regulation during T cell development}, url = {http://dx.doi.org/10.1073/pnas.0800810105}, volume = {105}, year = {2008} }

TY - JOUR ID - citeulike:2520243 L3 - citeulike-article-id:2520243 TI - Nucleoprotein structure of the CD4 locus: Implications for the mechanisms underlying CD4 regulation during T cell development JF - Proceedings of the National Academy of Sciences VL - 105 IS - 10 SP - 3873 EP - 3878 N2 - The CD4 gene is regulated in a stage-specific manner during T cell development, being repressed in CD4CD8 double-negative (DN) and CD8 cells, but expressed in CD4+CD8+ double-positive (DP) and CD4 cells. Furthermore, the expression/repression pattern is reversible in developing (DN and DP) thymocytes, but irreversible in mature (CD4 and CD8) T cells. Here, we explored the molecular mechanisms underlying this complex mode of regulation by examining the nucleoprotein structure of the CD4 locus throughout T cell development and in DN cells lacking the CD4 silencer. In DN cells, the CD4 enhancer is preloaded with multiple transcription activators, but p300 recruitment is impaired by the silencer that is associated with the repressor Runx1. DP cells achieve high-level CD4 expression via a combination of CD4 derepression and true activation, but Runx1 remains bound to the silencer that retains an open chromatin configuration. In CD4 cells, Runx1 dissociates from the silencer that has become less accessible, and CD4 transcription appears to be achieved via a mechanism distinct from that operating in DP cells. In CD8 cells, the CD4 promoter becomes incorporated into heterochromatin-like structure. Our data shed light on the molecular basis of CD4 regulation and provide a conceptual framework for understanding how the same regulatory elements can mediate both reversible and irreversible CD4 regulation. 10.1073/pnas.0800810105 AU - Yu, Ming AU - Wan, Mimi AU - Zhang, Jianmin AU - Wu, Jie AU - Khatri, Rohini AU - Chi, Tian PY - 2008/03/11/ UR - http://dx.doi.org/10.1073/pnas.0800810105 ER -