The transcriptional co-activator protein p100 recruits histone acetyltransferase activity to STAT6 and mediates interaction between the CREB-binding protein and STAT6.
STAT6 is a critical regulator of transcription for interleukin-4 (IL-4)-induced genes. Activation of gene expression involves recruitment of coactivator proteins that function as bridging factors connecting sequence-specific transcription factors to the basal transcription machinery, and as chromatin-modifying enzymes. Coactivator proteins CBP/p300 have been implicated in regulation of transcription in all ... STATs. CBP is also required for STAT6-mediated gene activation, but the underlying molecular mechanisms are still elusive. In this study we investigated the mechanisms by which STAT6 recruits CBP and chromatin-modifying activities to the promoter. Our results indicate that while STAT1-interacted directly with CBP, the interaction between STAT6 and CBP was found to be mediated through p100 protein, a coactivator protein that has previously been shown to stimulate the transcription of IL-4-induced genes. The staphylococcal nuclease-like (SN)-domains of p100 directly interacted with amino acids 1099-1758 of CBP, while p100 did not associate with SRC-1, another coactivator of STAT6. p100 was found to recruit histone acetyltransferase (HAT) activity to STAT6 in vivo. Chromatin immunoprecipitation studies demonstrated that p100 increases the STAT6-p100-CBP ternary complex formation in the human Igepsilon promoter. p100 also increased the amount of acetylated histone H4 at the Igepsilon promoter, and siRNAs directed against p100 effectively inhibited Igepsilon reporter gene expression. Our results suggest that p100 has an important role in the assembly of STAT6 transcriptosome, and that p100 stimulates IL-4-dependent transcription by mediating interaction between STAT6 and CBP and recruiting chromatin modifying activities to STAT6-responsive promoters.
Mesh Terms:
Acetyltransferases, Animals, COS Cells, Cell Line, Chromatin, Chromatin Immunoprecipitation, Genes, Reporter, Glutathione Transferase, Hela Cells, Histone Acetyltransferases, Humans, Immunoprecipitation, Interleukin-4, Microscopy, Confocal, Models, Biological, Nuclear Proteins, Plasmids, Promoter Regions, Genetic, Protein Binding, Protein Structure, Tertiary, RNA, Small Interfering, STAT6 Transcription Factor, Trans-Activators, Transcription, Genetic
Acetyltransferases, Animals, COS Cells, Cell Line, Chromatin, Chromatin Immunoprecipitation, Genes, Reporter, Glutathione Transferase, Hela Cells, Histone Acetyltransferases, Humans, Immunoprecipitation, Interleukin-4, Microscopy, Confocal, Models, Biological, Nuclear Proteins, Plasmids, Promoter Regions, Genetic, Protein Binding, Protein Structure, Tertiary, RNA, Small Interfering, STAT6 Transcription Factor, Trans-Activators, Transcription, Genetic
J. Biol. Chem.
Date: Apr. 15, 2005
PubMed ID: 15695802
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