Kim, J. H., Ebersole, T., Kouprina, N., Noskov, V. N., Ohzeki, J., Masumoto, H., Mravinac, B., Sullivan, B. A., Pavlicek, A., Dovat, S., Pack, S. D., Kwon, Y. W., Flanagan, P. T., Loukinov, D., Lobanenkov, V., Larionov, V.
Human Gamma-satellite DNA Maintains Open Chromatin Structure and Protects a Transgene from Epigenetic Silencing
Genome Res. 2009 Apr 01; 19(4): 533-44.
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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