The human SWI/SNF complex associates with RUNX1 to control transcription of hematopoietic target genes

Rachit Bakshi, Mohammad Q. Hassan, Jitesh Pratap, Jane B. Lian, Martin A. Montecino, Andre J. Van Wijnen, Janet L. Stein, Anthony N. Imbalzano, Gary S. Stein

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

The acute myeloid leukemia 1 (AML1, RUNX1) transcription factor is a key regulator of hematopoietic differentiation that forms multi-protein complexes with co-regulatory proteins. These complexes are assembled at target gene promoters in nuclear microenvironments to mediate phenotypic gene expression and chromatin-related epigenetic modifications. Here, immunofluorescence microscopy and biochemical assays are used to show that RUNX1 associates with the human ATP-dependent SWI/SNF chromatin remodeling complex. The SWI/SNF subunits BRG1 and INI1 bind in vivo to RUNX1 target gene promoters (e.g., GMCSF, IL3, MCSF-R, MIP, and p21). These interactions correlate with histone modifications characteristic of active chromatin, including acetylated H4 and dimethylated H3 lysine 4. Downregulation of RUNX1 by RNA interference diminishes the binding of BRG1 and INI1 at selected target genes. Taken together, our findings indicate that RUNX1 interacts with the human SWI/SNF complex to control hematopoietic-specific gene expression.

Original languageEnglish (US)
Pages (from-to)569-576
Number of pages8
JournalJournal of Cellular Physiology
Volume225
Issue number2
DOIs
StatePublished - Nov 2010

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Bakshi, R., Hassan, M. Q., Pratap, J., Lian, J. B., Montecino, M. A., Van Wijnen, A. J., Stein, J. L., Imbalzano, A. N., & Stein, G. S. (2010). The human SWI/SNF complex associates with RUNX1 to control transcription of hematopoietic target genes. Journal of Cellular Physiology, 225(2), 569-576. https://doi.org/10.1002/jcp.22240