Reconfiguration of genomic anchors upon transcriptional activation of the human major histocompatibility complex

  1. Diego Ottaviani1,2,
  2. Elliott Lever2,6,
  3. Richard Mitter1,6,
  4. Tania Jones2,
  5. Tim Forshew2,
  6. Rossitza Christova2,
  7. Eleni M. Tomazou3,
  8. Vardhman K. Rakyan2,
  9. Stephen A. Krawetz4,
  10. Adrian E. Platts4,
  11. Badmavady Segarane2,
  12. Stephan Beck5 and
  13. Denise Sheer2,7
  1. 1 Cancer Research UK London Research Institute, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom;
  2. 2 Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London E1 2AT, United Kingdom;
  3. 3 The Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom;
  4. 4 The Center for Molecular Medicine and Genetics and Department of Obstetrics and Gynecology, Wayne State University School of Medicine, C.S. Mott Center, Detroit, Michigan 48201, USA;
  5. 5 UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom
  1. 6 These authors contributed equally to this work.

Abstract

The folding of chromatin into topologically constrained loop domains is essential for genomic function. We have identified genomic anchors that define the organization of chromatin loop domains across the human major histocompatibility complex (MHC). This locus contains critical genes for immunity and is associated with more diseases than any other region of the genome. Classical MHC genes are expressed in a cell type-specific pattern and can be induced by cytokines such as interferon-gamma (IFNG). Transcriptional activation of the MHC was associated with a reconfiguration of chromatin architecture resulting from the formation of additional genomic anchors. These findings suggest that the dynamic arrangement of genomic anchors and loops plays a role in transcriptional regulation.

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