Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 9, Pages 3189-3194Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0611419104
Keywords
chromatin; epigenetic control; mitosis; cell division
Categories
Funding
- NCI NIH HHS [P01CA82834, P01 CA082834] Funding Source: Medline
- NIAMS NIH HHS [P01AR48818, P01 AR048818, R01 AR039588, T32 AR07572, R01 AR049069, AR39588, AR049069, T32 AR007572] Funding Source: Medline
- NIDDK NIH HHS [P30 DK32520, P30 DK032520] Funding Source: Medline
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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.
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