Human gamma-satellite DNA maintains open chromatin structure and protects a transgene from epigenetic silencing

  1. Jung-Hyun Kim1,
  2. Thomas Ebersole1,
  3. Natalay Kouprina1,
  4. Vladimir N. Noskov1,
  5. Jun-Ichirou Ohzeki1,
  6. Hiroshi Masumoto1,
  7. Brankica Mravinac2,
  8. Beth A. Sullivan2,
  9. Adam Pavlicek3,
  10. Sinisa Dovat4,
  11. Svetlana D. Pack5,
  12. Yoo-Wook Kwon5,
  13. Patrick T. Flanagan5,
  14. Dmitri Loukinov5,
  15. Victor Lobanenkov5 and
  16. Vladimir Larionov1,6
  1. 1 Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892, USA;
  2. 2 Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina 27708, USA;
  3. 3 Structural and Computational Biology, Pfizer Global Research and Development, La Jolla Laboratories, San Diego, California 92121, USA;
  4. 4 Department of Pediatrics, University of Wisconsin, Madison, Wisconsin 90095, USA;
  5. 5 Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20815, USA

    Abstract

    The role of repetitive DNA sequences in pericentromeric regions with respect to kinetochore/heterochromatin structure and function is poorly understood. Here, we use a mouse erythroleukemia cell (MEL) system for studying how repetitive DNA assumes or is assembled into different chromatin structures. We show that human gamma-satellite DNA arrays allow a transcriptionally permissive chromatin conformation in an adjacent transgene and efficiently protect it from epigenetic silencing. These arrays contain CTCF and Ikaros binding sites. In MEL cells, this gamma-satellite DNA activity depends on binding of Ikaros proteins involved in differentiation along the hematopoietic pathway. Given our discovery of gamma-satellite DNA in pericentromeric regions of most human chromosomes and a dynamic chromatin state of gamma-satellite arrays in their natural location, we suggest that gamma-satellite DNA represents a unique region of the functional centromere with a possible role in preventing heterochromatin spreading beyond the pericentromeric region.

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    This Article

    1. Published in Advance January 13, 2009, doi: 10.1101/gr.086496.108 Genome Res. 19: 533-544

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