SWI/SNF-independent nuclease hypersensitivity and an increased level of histone acetylation at the P1 promoter accompany active transcription of the bone master gene Runx2
Authors
Cruzat, FernandoHenriquez, Berta
Villagra, Alejandro
Hepp, Matias
Lian, Jane B.
Van Wijnen, Andre J.
Stein, Janet L.
Imbalzano, Anthony N.
Stein, Gary S.
Montecino, Martin A.
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2009-08-24Keywords
AcetylationAnimals
Bone Morphogenetic Protein 2
Cell Differentiation
Cell Line
Chromatin Assembly and Disassembly
Chromosomal Proteins, Non-Histone
Core Binding Factor Alpha 1 Subunit
Deoxyribonucleases
Gene Expression Regulation
Histones
Mice
Osteoblasts
*Promoter Regions, Genetic
Protein Isoforms
Transcription Factors
*Transcription, Genetic
Cell Biology
Metadata
Show full item recordAbstract
The Runx2 transcription factor is essential for skeletal development as it regulates expression of several key bone-related genes. Multiple lines of evidence indicate that expression of the Runx2/p57 isoform in osteoblasts is controlled by the distal P1 promoter. Alterations of chromatin structure are often associated with transcription and can be mediated by members of the SWI/SNF family of chromatin remodeling complexes, or by transcriptional coactivators that possess enzymatic activities that covalently modify structural components of the chromatin. Here, we report that a specific chromatin remodeling process at the proximal region (residues -400 to 35) of the Runx2 gene P1 promoter accompanies transcriptional activity in osteoblasts. This altered chromatin organization is reflected by the presence of two DNase I hypersensitive sites that span key regulatory elements for Runx2/p57 transcription. Chromatin remodeling and transcription of the Runx2 gene are associated with elevated levels of histone acetylation at the P1 promoter region and binding of active RNA polymerase II and are independent of the activity of the SWI/SNF chromatin remodeling complex. Changes in chromatin organization at the P1 promoter are stimulated during differentiation of C2C12 mesenchymal cells to the osteoblastic lineage by treatment with BMP2. Together, our results support a model in which changes in chromatin organization occur at very early stages of mesenchymal differentiation to facilitate subsequent expression of the Runx2/p57 isoform in osteoblastic cells.Source
Biochemistry. 2009 Aug 4;48(30):7287-95. Link to article on publisher's siteDOI
10.1021/bi9004792Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49603PubMed ID
19545172Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1021/bi9004792