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 Ohzeki2,
  6. Hiroshi Masumoto2,
  7. Brankica Mravinac3,
  8. Beth A. Sullivan3,
  9. Adam Pavlicek4,
  10. Sinisa Dovat5,
  11. Svetlana D. Pack6,
  12. Yoo-Wook Kwon6,
  13. Patrick T. Flanagan6,
  14. Dmitri Loukinov6,
  15. Victor Lobanenkov6 and
  16. Vladimir Larionov17
  1. 1 NIH;
  2. 2 National Cancer Institute;
  3. 3 Duke University;
  4. 4 Pfizer Global Research and Development;
  5. 5 University of Wisconsin;
  6. 6 National Institute of Allergy and Infectious Diseases

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 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. 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.

Footnotes

    • Received September 16, 2008.
    • Accepted December 17, 2008.
ACCEPTED MANUSCRIPT

This Article

  1. Published in Advance January 13, 2009, doi: 10.1101/gr.086496.108 Genome Res. gr.086496.108 Copyright © 2009, Cold Spring Harbor Laboratory Press

Article Category

Share

Preprint Server



Current Issue

  1. January 2026, 36 (1)
  1. Current Issue
  1. Alert me to new issues of Genome Research