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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Activation-dependent intrachromosomal interactions formed by the TNF gene promoter and two distal enhancers
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Activation-dependent intrachromosomal interactions formed by the TNF gene promoter and two distal enhancers

机译：Activation-dependent intrachromosomal interactions formed by the TNF gene promoter and two distal enhancers

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摘要

Here we provide a mechanism for specific, efficient transcription of the TNF gene and, potentially, other genes residing within multi-gene loci. We identify and characterize highly conserved noncoding elements flanking the TNF gene, which undergo activation-dependent intrachromosomal interactions. These elements, hypersensitive site (HSS)-9 and HSS+3 (9 kb upstream and 3 kb downstream of the TNF gene, respectively), contain DNase I hypersensitive sites in naive, T helper 1, and T helper 2 primary T cells. Both HSS-9 and HSS+3 inducibly associate with acetylated histones, indicative of chromatin remodeling, bind the transcription factor nuclear factor of activated T cells (NFAT)p in vitro and in vivo, and function as enhancers of NFAT-dependent transactivation mediated by the TNF promoter. Using the chromosome conformation capture assay, we demonstrate that upon T cell activation intrachromosomal looping occurs in the TNF locus. HSS-9 and HSS+3 each associate with the TNF promoter and with each other, circularizing the TNF gene and bringing NFAT-containing nucleoprotein complexes into close proximity. TNF gene regulation thus reveals a mode of intrachromosomal interaction that combines a looped gene topology with interactions between enhancers and a gene promoter.

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