Differentiation-dependent association of phosphorylated extracellular signal-regulated kinase with the chromatin of osteoblast-related genes
dc.contributor.author | Li, Yan | en_US |
dc.contributor.author | Ge, Chunxi | en_US |
dc.contributor.author | Franceschi, Renny T. | en_US |
dc.date.accessioned | 2010-02-02T15:29:58Z | |
dc.date.available | 2011-03-01T16:26:42Z | en_US |
dc.date.issued | 2010-01 | en_US |
dc.identifier.citation | Li, Yan; Ge, Chunxi; Franceschi, Renny T (2010). "Differentiation-dependent association of phosphorylated extracellular signal-regulated kinase with the chromatin of osteoblast-related genes." Journal of Bone and Mineral Research 25(1): 154-163. <http://hdl.handle.net/2027.42/64899> | en_US |
dc.identifier.issn | 0884-0431 | en_US |
dc.identifier.issn | 1523-4681 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/64899 | |
dc.description.abstract | The ERK/MAP kinase pathway is an important regulator of gene expression and differentiation in postmitotic cells. To understand how this pathway controls gene expression in bone, we examined the subnuclear localization of P-ERK in differentiating osteoblasts. Induction of differentiation was accompanied by increased ERK phosphorylation and expression of osteoblast-related genes, including osteocalcin ( Bglap2 ) and bone sialoprotein ( Ibsp ). Confocal immunofluorescence microscopy revealed that P-ERK colocalized with the RUNX2 transcription factor in the nuclei of differentiating cells. Interestingly, a portion of this nuclear P-ERK was directly bound to the proximal promoter regions of Bglap2 and Ibsp . Furthermore, the level of P-ERK binding to chromatin increased with differentiation, whereas RUNX2 binding remained relatively constant. The P-ERK-chromatin interaction was seen only in RUNX2-positive cells, required intact RUNX2-selective enhancer sequences, and was blocked with MAPK inhibition. These studies show for the first time that RUNX2 specifically targets P-ERK to the chromatin of osteoblast-related genes, where it may phosphorylate multiple substrates, including RUNX2, resulting in altered chromatin structure and gene expression. © 2010 American Society for Bone and Mineral Research | en_US |
dc.format.extent | 443275 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Anatomy and Physiology and CELL BIOLOGY | en_US |
dc.subject.other | Endocrinology | en_US |
dc.title | Differentiation-dependent association of phosphorylated extracellular signal-regulated kinase with the chromatin of osteoblast-related genes | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialities | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry | en_US |
dc.contributor.affiliationum | Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry | en_US |
dc.contributor.affiliationum | Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry ; Department of Biological Chemistry, University of Michigan School of Medicine, 1011 N. University Ave., Ann Arbor, MI, USA ; Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, 1011 North University Ave., Ann Arbor, MI 48109, USA. | en_US |
dc.identifier.pmid | 19580458 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/64899/1/90705_ftp.pdf | |
dc.identifier.doi | 10.1359/jbmr.090705 | en_US |
dc.identifier.source | Journal of Bone and Mineral Research | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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