Title |
Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization
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Published in |
Genome Biology, December 2015
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DOI | 10.1186/s13059-015-0832-9 |
Pubmed ID | |
Authors |
Tatyana Kuznetsova, Shuang-Yin Wang, Nagesha A. Rao, Amit Mandoli, Joost H. A. Martens, Nils Rother, Aafke Aartse, Laszlo Groh, Eva M. Janssen-Megens, Guoliang Li, Yijun Ruan, Colin Logie, Hendrik G. Stunnenberg |
Abstract |
The impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from remodeling of higher order chromatin architecture by activated transcription factors to recruitment of activated transcription factors to pre-established long-range interactions. Using circular chromosome conformation capture coupled with next generation sequencing and high-resolution chromatin interaction analysis by paired-end tag sequencing of P300, we observed agonist-induced changes in long-range chromatin interactions, and uncovered interconnected enhancer-enhancer hubs spanning up to one megabase. The vast majority of activated glucocorticoid receptor and nuclear factor kappa-b appeared to join pre-existing P300 enhancer hubs without affecting the chromatin conformation. In contrast, binding of the activated transcription factors to loci with their consensus response elements led to the increased formation of an active epigenetic state of enhancers and a significant increase in long-range interactions within pre-existing enhancer networks. De novo enhancers or ligand-responsive enhancer hubs preferentially interacted with ligand-induced genes. We demonstrate that, at a subset of genomic loci, ligand-mediated induction leads to active enhancer formation and an increase in long-range interactions, facilitating efficient regulation of target genes. Therefore, our data suggest an active role of signal-dependent transcription factors in chromatin and long-range interaction remodeling. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 5 | 36% |
United Kingdom | 2 | 14% |
France | 1 | 7% |
Canada | 1 | 7% |
Unknown | 5 | 36% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 8 | 57% |
Scientists | 5 | 36% |
Science communicators (journalists, bloggers, editors) | 1 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 2 | 2% |
Germany | 1 | 1% |
Netherlands | 1 | 1% |
Canada | 1 | 1% |
Greece | 1 | 1% |
United States | 1 | 1% |
Unknown | 87 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 25 | 27% |
Student > Ph. D. Student | 25 | 27% |
Student > Master | 14 | 15% |
Student > Doctoral Student | 5 | 5% |
Student > Bachelor | 4 | 4% |
Other | 13 | 14% |
Unknown | 8 | 9% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 39 | 41% |
Agricultural and Biological Sciences | 26 | 28% |
Engineering | 3 | 3% |
Neuroscience | 3 | 3% |
Computer Science | 3 | 3% |
Other | 9 | 10% |
Unknown | 11 | 12% |