| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Toronto Western Research Institute, University Health Network, Department of Ophthalmology and Vision Science, Vision Science Research Program, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada
IL-6 is an immunoregulatory cytokine with multiple functions in hemopoiesis, proliferation, and tumorigenesis. IL-6 triggers phosphorylation, dimerization, and nuclear translocation of STAT3, which binds to target promoters and activates transcription. Brahma-related gene 1 (BRG1), the enzymatic engine of the yeast-mating type-switching and sucrose-nonfermenting chromatin-remodeling complex, is essential for recruitment of STAT1 or STAT1/STAT2-containing complexes to IFN targets. We hypothesized that BRG1 might also be required for STAT3 recruitment. In this study, we show that induction of a subset of human IL-6-responsive genes is BRG1 dependent. BRG1 is constitutively present at these targets and is required for STAT3 recruitment, downstream histone modifications, and IL-6-induced chromatin remodeling. IL-6-induced recruitment of STAT3 to the IFN regulatory factor 1 promoter and subsequent mRNA synthesis is BRG1 dependent, even though IFN-
-mediated STAT1 recruitment to this locus is BRG1 independent. BRG1 also increased basal expression of IFN-induced transmembrane protein 3 and IFN--induced protein 16, and the basal chromatin accessibility at the promoter of IFN regulatory factor 1. The effect on basal expression was STAT3 independent, as revealed by small interfering RNA knockdown. Together with prior observations, these data reveal that BRG1 has a broad role in mediating STAT accessibility at multiple cytokine-responsive promoters and exposes promoter specific differences in both the effect of BRG1 on basal chromatin accessibility and on access of different STAT proteins to the same target.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the National Cancer Institute of Canada with funds from the Canadian Cancer Society. Z.N. was supported by fellowships from Ontario Graduate studentships, the Vision Science Research Program, the Frank Fletcher Memorial Fund, and the Dr. R. Dittakavi and Dr. P. Rao Graduate Award.
2 Address correspondence and reprint requests to Dr. Rod Bremner, Toronto Western Research Institute, MC6-424, Cellular and Molecular Division, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8. E-mail address: rbremner{at}uhnres.utoronto.ca
3 Abbreviations used in this paper: SWI/SNF, yeast mating type switching and sucrose nonfermenting; IRF1, IFN regulatory factor 1; qPCR, quantitative real-time PCR; IFI16, IFN--inducible protein 16; ChIP, chromatin immunoprecipitation; IP, immunoprecipitated; RSB, reticulocyte standard buffer; siRNA, small interfering RNA; IFITM3, IFN-induced transmembrane protein 3; MNDA, myeloid cell nuclear differentiation Ag.
This article has been cited by other articles:
|
|
 |
|
  T. Hou, S. Ray, and A. R. Brasier The Functional Role of an Interleukin 6-inducible CDK9{middle dot}STAT3 Complex in Human {gamma}-Fibrinogen Gene Expression J. Biol. Chem., December 21, 2007; 282(51): 37091 - 37102. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
