Kinetic profiles of p300 occupancy in vivo predict common features of promoter structure and coactivator recruitment.

Understanding the language encrypted in the gene regulatory regions of the human genome is a challenging goal for the genomic era. Although customary extrapolations from steady-state mRNA levels have been effective, deciphering these regulatory codes will require additional empirical data sets that more closely reflect the dynamic progression of molecular events responsible for inducible transcription. We describe an approach using chromatin immunoprecipitation to profile the kinetic occupancy of the transcriptional coactivator and histone acetyltransferase p300 at numerous mitogen-induced genes in activated T cells.

Targeting combinatorial transcriptional complex assembly at specific modules within the interleukin-2 promoter by the immunosuppressant SB203580.

The proximal promoter sequence of the interleukin-2 (IL-2) gene contains a series of composite sites or modules that controls much of its responsiveness to environmental stimuli. The integrated targeting of these modules is therefore a major mode of regulation. This report describes how multiple functional hierarchies, required for the recruitment of the p300 co-activator to the CD28RE/AP1 (TRE) module of the IL-2 promoter, are selectively disrupted in human T-cells by the immunosuppressive and anti-inflammatory actions of the p38 mitogen-activated protein kinase inhibitor (MAPK), SB203580.

Cross-regulation of T cell growth factor expression by p53 and the Tax oncogene.

In this study, we demonstrate that p53 directly inhibits expression of the T cell growth factor (IL-2) in activated T cells. This repression is independent of the intrinsic transcriptional activity of p53 and is mediated by the Tax-responsive CD28RE-3'-12-O-tetradecanoylphorbol-13-acetate response element (AP1) element of the IL-2 promoter. Coexpression of the Tax oncogene causes full reversal of this repression through coordinate targeting of p300, CREB, and the NF-kappaB pathways.