Article abstract
Nature Immunology 9, 785 - 793 (2008)
Published online: 25 May 2008 | doi:10.1038/ni.1619
The chromatin-remodeling enzyme BRG1 coordinates CIITA induction through many interdependent distal enhancers
Zuyao Ni1,2, Mohamed Abou El Hassan1,2, Zhaodong Xu1, Tao Yu1 & Rod Bremner1
Abstract
The chromatin-remodeling enzyme BRG1 is critical for interferon-
(IFN-)-mediated gene induction. Promoter-proximal elements are sufficient to mediate BRG1 dependency at some IFN- targets. In contrast, we show here that at CIITA, which encodes the 'master regulator' of induction of major histocompatibility complex class II, distal elements conferred BRG1 dependency. At the uninduced locus, many sites formed BRG1-independent loops. One loop juxtaposed a far downstream element adjacent to a far upstream site. Notably, BRG1 was recruited to the latter site, which triggered the appearance of a histone 'mark' linked to activation. This subtle change was crucial, as subsequent IFN--induced recruitment of the transcription factors STAT1, IRF1 and p300, as well as histone modifications, accessibility and additional loops, showed BRG1 dependency. Like BRG1, each remote element was critical for the induction of CIITA expression. Thus, BRG1 regulates CIITA through many interdependent remote enhancers, not through the promoter alone.
- Genetics and Development Division, Toronto Western Research Institute, University Health Network. Department of Ophthalmology and Vision Sciences, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5T 2S8, Canada.
- These authors contributed equally to this work.
Correspondence to: Rod Bremner1 e-mail: rbremner@uhnres.utoronto.ca
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