title: Estrogen-induced chromatin decondensation and nuclear re-organization linked to regional epigenetic regulation in breast cancer.
abstract: BACKGROUND
  Epigenetic changes are being increasingly recognized as a prominent feature of cancer. This occurs not only at individual genes, but also over larger chromosomal domains. To investigate this, we set out to identify large chromosomal domains of epigenetic dysregulation in breast cancers.
  
  
  RESULTS
  We identify large regions of coordinate down-regulation of gene expression, and other regions of coordinate activation, in breast cancers and show that these regions are linked to tumor subtype. In particular we show that a group of coordinately regulated regions are expressed in luminal, estrogen-receptor positive breast tumors and cell lines. For one of these regions of coordinate gene activation, we show that regional epigenetic regulation is accompanied by visible unfolding of large-scale chromatin structure and a repositioning of the region within the nucleus. In MCF7 cells, we show that this depends on the presence of estrogen.
  
  
  CONCLUSIONS
  Our data suggest that the liganded estrogen receptor is linked to long-range changes in higher-order chromatin organization and epigenetic dysregulation in cancer. This may suggest that as well as drugs targeting histone modifications, it will be valuable to investigate the inhibition of protein complexes involved in chromatin folding in cancer cells.
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK. sehrishrafique@hotmail.com.|Edinburgh Breakthrough Research Unit and Edinburgh Cancer Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh, Scotland, EH4 2XU, UK. sehrishrafique@hotmail.com.
authors.forename: Sehrish
authors.initials: S
authors.lastname: Rafique
authors.affiliation: Edinburgh Breakthrough Research Unit and Edinburgh Cancer Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh, Scotland, EH4 2XU, UK. jeremy.thomas@luht.scot.nhs.uk.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Thomas
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK. Duncan.Sproul@igmm.ed.ac.uk.|Edinburgh Breakthrough Research Unit and Edinburgh Cancer Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh, Scotland, EH4 2XU, UK. Duncan.Sproul@igmm.ed.ac.uk.
authors.forename: Duncan
authors.initials: D
authors.lastname: Sproul
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK. Wendy.Bickmore@igmm.ed.ac.uk.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Bickmore
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics; D002843:Chromatin / Q000737:chemistry*; D044127:Epigenesis, Genetic; D004967:Estrogens / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D011960:Receptors, Estrogen / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D004967:Estrogens; D011960:Receptors, Estrogen