Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2

Daniel W. Young, Mohammad Q. Hassan, Xiao Qing Yang, Mario Galindo, Amjad Javed, Sayyed K. Zaidi, Paul Furcinitti, David Lapointe, Martin Montecino, Jane B. Lian, Janet L. Stein, Andre J. Van Wijnen, Gary S. Stein

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

During cell division, cessation of transcription is coupled with mitotic chromosome condensation. A fundamental biological question is how gene expression patterns are retained during mitosis to ensure the phenotype of progeny cells. We suggest that cell fate-determining transcription factors provide an epigenetic mechanism for the retention of gene expression patterns during cell division. Runx proteins are lineage-specific transcription factors that are essential for hematopoietic, neuronal, gastrointestinal, and osteogenic cell fates. Here we show that Runx2 protein is stable during cell division and remains associated with chromosomes during mitosis through sequence-specific DNA binding. Using siRNA-mediated silencing, mitotic cell synchronization, and expression profiling, we identify Runx2-regulated genes that are modulated postmitotically. Novel target genes involved in cell growth and differentiation were validated by chromatin immunoprecipitation. Importantly, we find that during mitosis, when transcription is shut down, Runx2 selectively occupies target gene promoters, and Runx2 deficiency alters mitotic histone modifications. We conclude that Runx proteins have an active role in retaining phenotype during cell division to support lineage-specific control of gene expression in progeny cells.

Original languageEnglish (US)
Pages (from-to)3189-3194
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number9
DOIs
StatePublished - Feb 27 2007

Keywords

  • Cell division
  • Chromatin
  • Epigenetic control
  • Mitosis

ASJC Scopus subject areas

  • General

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    Young, D. W., Hassan, M. Q., Yang, X. Q., Galindo, M., Javed, A., Zaidi, S. K., Furcinitti, P., Lapointe, D., Montecino, M., Lian, J. B., Stein, J. L., Van Wijnen, A. J., & Stein, G. S. (2007). Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2. Proceedings of the National Academy of Sciences of the United States of America, 104(9), 3189-3194. https://doi.org/10.1073/pnas.0611419104