| COACTIVATORS AND COREPRESSORS OF NF-KB IN IkB ALPHA GENE PROMOTER | |||||||||||
Abstract | |||||||||||
| In this study, we investigated recruitment of coactivators (SRC-1, SRC-2 and SRC-3) and corepressors (HDAC1, HDAC2, HDAC3, SMRT and NCoR) to the IkBα gene promoter after NF-kB activation by TNF-α. Our data from ChIP assay suggest that coactivators and corepressors are simultaneously recruited to the promoter, and their binding to the promoter DNA is oscillated in HEK293 cells. SRC-1, SRC-2 and SRC-3 all enhanced IkBα transcription. However, the interaction of each coactivator with the promoter exhibited different patterns. After TNF-α treatment, SRC-1 signal was increased gradually, but SRC-2 signal was reduced immediately, suggesting replacement of SRC-2 by SRC-1. SRC-3 signal was increased at 30 minutes, reduced at 60 minutes, and then increased again at 120 minutes, suggesting an oscillation of SRC-3. The corepressors were recruited to the promoter together with the coactivators. The binding pattern suggests that the corepressor proteins formed two types of corepressor complexes, SMRT/HDAC1 and NCoR/HDAC3. The two complexes exhibited a switch at 30 and 60 minutes. The functions of corepressor proteins were confirmed by gene overexpression and RNAi-mediated gene knockdown. These data suggest that gene transactivation by the transcription factor NF-kB is subject to the regulation of a dynamic balance between the coactivators and corepressors. This model may represent a mechanism for integration of extracellular signals into a precise control of gene transcription. | |||||||||||
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