GSBS Student Publications

Title

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

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology; Department of Cancer Biology; Program in Molecular Medicine; Information Services

Date

3-16-2007

Document Type

Article

Medical Subject Headings

Blotting, Western; Cell Differentiation; Cell Line, Tumor; Chromatin Immunoprecipitation; Chromosomes, Human; Core Binding Factor Alpha 1 Subunit; Electrophoretic Mobility Shift Assay; Epigenesis, Genetic; Gene Expression Profiling; Gene Expression Regulation; Humans; Microscopy, Fluorescence; Mitosis; Promoter Regions (Genetics); RNA Interference

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3189-94. Epub 2007 Feb 20. Link to article on publisher's site

DOI of Published Version

10.1073/pnas.0611419104

Related Resources

Link to Article in PubMed

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

17360627