Subnuclear targeting of the Runx3 tumor suppressor and its epigenetic association with mitotic chromosomes

Sandhya Pande, Syed A. Ali, Christopher Dowdy, Sayyed K. Zaidi, Kosei Ito, Yoshiaki Ito, Martin A. Montecino, Jane B. Lian, Janet L. Stein, Andre J van Wijnen, Gary S. Stein

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)473-479
Number of pages7
JournalJournal of Cellular Physiology
Volume218
Issue number3
DOIs
StatePublished - Mar 2009
Externally publishedYes

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Core Binding Factor Alpha 2 Subunit
Core Binding Factor Alpha 1 Subunit
Interphase
Chromosomes
Epigenomics
Tumors
Genes
Mitosis
Association reactions
Core Binding Factor Alpha 3 Subunit
Core Binding Factor alpha Subunits
RNA Polymerase I
Tumor Suppressor Proteins
Neoplasms
RNA Polymerase II
Cell growth
Bioactivity
Nuclear Matrix
Genetic Promoter Regions
Gene expression

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Subnuclear targeting of the Runx3 tumor suppressor and its epigenetic association with mitotic chromosomes. / 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.

In: Journal of Cellular Physiology, Vol. 218, No. 3, 03.2009, p. 473-479.

Research output: Contribution to journalArticle

Pande, S, Ali, SA, Dowdy, C, Zaidi, SK, Ito, K, Ito, Y, Montecino, MA, Lian, JB, Stein, JL, van Wijnen, AJ & Stein, GS 2009, 'Subnuclear targeting of the Runx3 tumor suppressor and its epigenetic association with mitotic chromosomes', Journal of Cellular Physiology, vol. 218, no. 3, pp. 473-479. https://doi.org/10.1002/jcp.21630
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. / Subnuclear targeting of the Runx3 tumor suppressor and its epigenetic association with mitotic chromosomes. In: Journal of Cellular Physiology. 2009 ; Vol. 218, No. 3. pp. 473-479.
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