Pbx1 represses osteoblastogenesis by blocking Hoxa10-mediated recruitment of chromatin remodeling factors
Authors
Gordon, Jonathan A. R.Hassan, Mohammad Q.
Saini, Sharanjot
Montecino, Martin A.
Van Wijnen, Andre J.
Stein, Gary S.
Stein, Janet L.
Lian, Jane B.
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2010-07-01Keywords
3T3 CellsAnimals
Base Sequence
Cell Differentiation
Cell Line
Chromatin Assembly and Disassembly
Gene Expression Regulation, Developmental
Homeodomain Proteins
Humans
Integrin-Binding Sialoprotein
Mice
Models, Biological
Multipotent Stem Cells
Mutation
Osteoblasts
Osteocalcin
Osteogenesis
Promoter Regions, Genetic
RNA, Small Interfering
Rats
Sialoglycoproteins
Transcription Factors
Transcriptional Activation
Cell Biology
Metadata
Show full item recordAbstract
Abdominal-class homeodomain-containing (Hox) factors form multimeric complexes with TALE-class homeodomain proteins (Pbx, Meis) to regulate tissue morphogenesis and skeletal development. Here we have established that Pbx1 negatively regulates Hoxa10-mediated gene transcription in mesenchymal cells and identified components of a Pbx1 complex associated with genes in osteoblasts. Expression of Pbx1 impaired osteogenic commitment of C3H10T1/2 multipotent cells and differentiation of MC3T3-E1 preosteoblasts. Conversely, targeted depletion of Pbx1 by short hairpin RNA (shRNA) increased expression of osteoblast-related genes. Studies using wild-type and mutated osteocalcin and Bsp promoters revealed that Pbx1 acts through a Pbx-binding site that is required to attenuate gene activation by Hoxa10. Chromatin-associated Pbx1 and Hoxa10 were present at osteoblast-related gene promoters preceding gene expression, but only Hoxa10 was associated with these promoters during transcription. Our results show that Pbx1 is associated with histone deacetylases normally linked with chromatin inactivation. Loss of Pbx1 from osteoblast promoters in differentiated osteoblasts was associated with increased histone acetylation and CBP/p300 recruitment, as well as decreased H3K9 methylation. We propose that Pbx1 plays a central role in attenuating the ability of Hoxa10 to activate osteoblast-related genes in order to establish temporal regulation of gene expression during osteogenesis.Source
Gordon, Jonathan A. R., Hassan, Mohammad Q., Saini, Sharanjot, Montecino, Martin, van Wijnen, Andre J., Stein, Gary S., Stein, Janet L., Lian, Jane B. Pbx1 Represses Osteoblastogenesis by Blocking Hoxa10-Mediated Recruitment of Chromatin Remodeling Factors. Mol. Cell. Biol. 2010 30: 3531-3541. doi:10.1128/MCB.00889-09. Link to article on publisher's websiteDOI
10.1128/MCB.00889-09Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49564PubMed ID
20439491Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/MCB.00889-09