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Subnuclear targeting of the Runx3 tumor suppressor and its epigenetic association with mitotic chromosomes
Author(s) -
Pande Sandhya,
Ali Syed A.,
Dowdy Christopher,
Zaidi Sayyed K.,
Ito Kosei,
Ito Yoshiaki,
Montecino Martin A.,
Lian Jane B.,
Stein Janet L.,
van Wijnen Andre J.,
Stein Gary S.
Publication year - 2009
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21630
Subject(s) - biology , mitosis , interphase , microbiology and biotechnology , epigenetics , chromatin , cell cycle , chromatin immunoprecipitation , chromatin remodeling , promoter , gene expression , gene , genetics
Runx proteins are tissue‐specific transcriptional scaffolds that organize and assemble regulatory complexes at strategic sites of target gene promoters and at intranuclear foci to govern activation or repression. During interphase, fidelity of intranuclear targeting supports the biological activity of Runx1 and Runx2 proteins. Both factors regulate genes involved in cell cycle control and cell growth (e.g., rRNA genes), as well as lineage commitment. Here, we have examined the subcellular regulatory properties of the third Runx member, the tumor suppressor protein Runx3, during interphase and mitosis. Using in situ cellular and biochemical approaches we delineated a subnuclear targeting signal that directs Runx3 to discrete transcriptional foci that are nuclear matrix associated. Chromatin immunoprecipitation results show that Runx3 occupies rRNA promoters during interphase. We also find that Runx3 remains associated with chromosomes during mitosis and localizes with nucleolar organizing regions (NORs), reflecting an interaction with epigenetic potential. Taken together, our study establishes that common mechanisms control the subnuclear distribution and activities of Runx1, Runx2, and Runx3 proteins to support RNA polymerase I and II mediated gene expression during interphase and mitosis. J. Cell. Physiol. 218: 473–479, 2009. © 2008 Wiley‐Liss, Inc.