title: Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Biology, Faculty of Science Nijmegen, Radboud University, Nijmegen, The Netherlands. T.Kuznetsova@ncmls.ru.nl.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Kuznetsova
authors.affiliation: Department of Molecular Biology, Faculty of Science Nijmegen, Radboud University, Nijmegen, The Netherlands. S.Wang@ncmls.ru.nl.
authors.forename: Shuang-Yin
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology, Faculty of Science Nijmegen, Radboud University, Nijmegen, The Netherlands. nagesha.nrao@gmail.com.
authors.forename: Nagesha A
authors.initials: NA
authors.lastname: Rao
authors.affiliation: Department of Molecular Biology, Faculty of Science Nijmegen, Radboud University, Nijmegen, The Netherlands. A.Mandoli@ncmls.ru.nl.
authors.forename: Amit
authors.initials: A
authors.lastname: Mandoli
authors.affiliation: Department of Molecular Biology, Faculty of Science Nijmegen, Radboud University, Nijmegen, The Netherlands. J.Martens@ncmls.ru.nl.
authors.forename: Joost H A
authors.initials: JH
authors.lastname: Martens
authors.affiliation: Department of Molecular Biology, Faculty of Science Nijmegen, Radboud University, Nijmegen, The Netherlands. n.rother@gmx.de.
authors.forename: Nils
authors.initials: N
authors.lastname: Rother
authors.affiliation: Department of Molecular Biology, Faculty of Science Nijmegen, Radboud University, Nijmegen, The Netherlands. aafke.aartse@gmail.com.
authors.forename: Aafke
authors.initials: A
authors.lastname: Aartse
authors.affiliation: Department of Molecular Biology, Faculty of Science Nijmegen, Radboud University, Nijmegen, The Netherlands. laszlogroh@gmail.com.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Groh
authors.affiliation: Department of Molecular Biology, Faculty of Science Nijmegen, Radboud University, Nijmegen, The Netherlands. e.janssen-megens@science.ru.nl.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Janssen-Megens
authors.affiliation: National Key Laboratory of Crop Genetic Improvement, College of Informatics, Huazhong Agricultural University, Wuhan, China. guoliang.li@mail.hzau.edu.cn.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Li
authors.affiliation: The Jackson Laboratory for Genomic Medicine, and Department of Genetic and Development Biology, University of Connecticut, 400 Farmington Ave., Farmington, CT, 06030, USA. yijun.ruan@jax.org.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Department of Molecular Biology, Faculty of Science Nijmegen, Radboud University, Nijmegen, The Netherlands. C.Logie@ncmls.ru.nl.
authors.forename: Colin
authors.initials: C
authors.lastname: Logie
authors.affiliation: Department of Molecular Biology, Faculty of Science Nijmegen, Radboud University, Nijmegen, The Netherlands. h.stunnenberg@ncmls.ru.nl.
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
mesh_terms: D001665:Binding Sites; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D053263:Gene Regulatory Networks; D008024:Ligands; D016328:NF-kappa B / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D002843:Chromatin; D008024:Ligands; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D050880:p300-CBP Transcription Factors