Reduced CpG methylation is associated with transcriptional activation of the bone-specific rat osteocalcin gene in osteoblasts

Alejandro Villagra, Jos Gutirrez, Roberto Paredes, Jos Sierra, Marcia Puchi, Maria Imschenetzky, Andre Van Wijnen, Jane Lian, Gary Stein, Janet Stein, Martin Montecino

Resultado de la investigación: Article

77 Citas (Scopus)

Resumen

Chromatin remodeling of the bone-specific rat osteocalcin (OC) gene accompanies the onset and increase in OC expression during osteoblast differentiation. In osseous cells expressing OC, the promoter region contains two nuclease hypersensitive sites that encompass the elements that regulate basal tissue-specific and vitamin D-enhanced OC transcription. Multiple lines of evidence indicate that DNA methylation is involved in maintaining a stable and condensed chromatin organization that represses eukaryotic transcription. Here we report that DNA methylation at the OC gene locus is associated with the condensed chromatin structure found in cells not expressing OC. In addition, we find that reduced CpG methylation of the OC gene accompanies active transcription in ROS 17/2.8 rat osteosarcoma cells. Interestingly, during differentiation of primary diploid rat osteoblasts in culture, as the OC gene becomes increasingly expressed, CpG methylation of the OC promoter is significantly reduced. Inhibition of OC transcription does not occur by a direct mechanism because in vitro methylated OC promoter DNA is still recognized by the key regulators Runx/Cbfa and the vitamin D receptor complex. Furthermore, CpG methylation affects neither basal nor vitamin D-enhanced OC promoter activity in transient expression experiments. Together, our results indicate that DNA methylation may contribute indirectly to OC transcriptional control in osteoblasts by maintaining a highly condensed and repressed chromatin structure.

Idioma originalEnglish
Páginas (desde-hasta)112-122
Número de páginas11
PublicaciónJournal of Cellular Biochemistry
Volumen85
N.º1
DOI
EstadoPublished - 2002

Huella dactilar

Methylation
Osteocalcin
Osteoblasts
Transcriptional Activation
Rats
Bone
Genes
Chemical activation
Bone and Bones
Transcription
Chromatin
DNA Methylation
Vitamin D
Calcitriol Receptors
Chromatin Assembly and Disassembly
Osteosarcoma
Diploidy
Cell culture
Genetic Promoter Regions

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Citar esto

Villagra, Alejandro ; Gutirrez, Jos ; Paredes, Roberto ; Sierra, Jos ; Puchi, Marcia ; Imschenetzky, Maria ; Van Wijnen, Andre ; Lian, Jane ; Stein, Gary ; Stein, Janet ; Montecino, Martin. / Reduced CpG methylation is associated with transcriptional activation of the bone-specific rat osteocalcin gene in osteoblasts. En: Journal of Cellular Biochemistry. 2002 ; Vol. 85, N.º 1. pp. 112-122.
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title = "Reduced CpG methylation is associated with transcriptional activation of the bone-specific rat osteocalcin gene in osteoblasts",
abstract = "Chromatin remodeling of the bone-specific rat osteocalcin (OC) gene accompanies the onset and increase in OC expression during osteoblast differentiation. In osseous cells expressing OC, the promoter region contains two nuclease hypersensitive sites that encompass the elements that regulate basal tissue-specific and vitamin D-enhanced OC transcription. Multiple lines of evidence indicate that DNA methylation is involved in maintaining a stable and condensed chromatin organization that represses eukaryotic transcription. Here we report that DNA methylation at the OC gene locus is associated with the condensed chromatin structure found in cells not expressing OC. In addition, we find that reduced CpG methylation of the OC gene accompanies active transcription in ROS 17/2.8 rat osteosarcoma cells. Interestingly, during differentiation of primary diploid rat osteoblasts in culture, as the OC gene becomes increasingly expressed, CpG methylation of the OC promoter is significantly reduced. Inhibition of OC transcription does not occur by a direct mechanism because in vitro methylated OC promoter DNA is still recognized by the key regulators Runx/Cbfa and the vitamin D receptor complex. Furthermore, CpG methylation affects neither basal nor vitamin D-enhanced OC promoter activity in transient expression experiments. Together, our results indicate that DNA methylation may contribute indirectly to OC transcriptional control in osteoblasts by maintaining a highly condensed and repressed chromatin structure.",
keywords = "CpG methylation, Osteocalcin, Transcription",
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year = "2002",
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Villagra, A, Gutirrez, J, Paredes, R, Sierra, J, Puchi, M, Imschenetzky, M, Van Wijnen, A, Lian, J, Stein, G, Stein, J & Montecino, M 2002, 'Reduced CpG methylation is associated with transcriptional activation of the bone-specific rat osteocalcin gene in osteoblasts', Journal of Cellular Biochemistry, vol. 85, n.º 1, pp. 112-122. https://doi.org/10.1002/jcb.10113

Reduced CpG methylation is associated with transcriptional activation of the bone-specific rat osteocalcin gene in osteoblasts. / Villagra, Alejandro; Gutirrez, Jos; Paredes, Roberto; Sierra, Jos; Puchi, Marcia; Imschenetzky, Maria; Van Wijnen, Andre; Lian, Jane; Stein, Gary; Stein, Janet; Montecino, Martin.

En: Journal of Cellular Biochemistry, Vol. 85, N.º 1, 2002, p. 112-122.

Resultado de la investigación: Article

TY - JOUR

T1 - Reduced CpG methylation is associated with transcriptional activation of the bone-specific rat osteocalcin gene in osteoblasts

AU - Villagra, Alejandro

AU - Gutirrez, Jos

AU - Paredes, Roberto

AU - Sierra, Jos

AU - Puchi, Marcia

AU - Imschenetzky, Maria

AU - Van Wijnen, Andre

AU - Lian, Jane

AU - Stein, Gary

AU - Stein, Janet

AU - Montecino, Martin

PY - 2002

Y1 - 2002

N2 - Chromatin remodeling of the bone-specific rat osteocalcin (OC) gene accompanies the onset and increase in OC expression during osteoblast differentiation. In osseous cells expressing OC, the promoter region contains two nuclease hypersensitive sites that encompass the elements that regulate basal tissue-specific and vitamin D-enhanced OC transcription. Multiple lines of evidence indicate that DNA methylation is involved in maintaining a stable and condensed chromatin organization that represses eukaryotic transcription. Here we report that DNA methylation at the OC gene locus is associated with the condensed chromatin structure found in cells not expressing OC. In addition, we find that reduced CpG methylation of the OC gene accompanies active transcription in ROS 17/2.8 rat osteosarcoma cells. Interestingly, during differentiation of primary diploid rat osteoblasts in culture, as the OC gene becomes increasingly expressed, CpG methylation of the OC promoter is significantly reduced. Inhibition of OC transcription does not occur by a direct mechanism because in vitro methylated OC promoter DNA is still recognized by the key regulators Runx/Cbfa and the vitamin D receptor complex. Furthermore, CpG methylation affects neither basal nor vitamin D-enhanced OC promoter activity in transient expression experiments. Together, our results indicate that DNA methylation may contribute indirectly to OC transcriptional control in osteoblasts by maintaining a highly condensed and repressed chromatin structure.

AB - Chromatin remodeling of the bone-specific rat osteocalcin (OC) gene accompanies the onset and increase in OC expression during osteoblast differentiation. In osseous cells expressing OC, the promoter region contains two nuclease hypersensitive sites that encompass the elements that regulate basal tissue-specific and vitamin D-enhanced OC transcription. Multiple lines of evidence indicate that DNA methylation is involved in maintaining a stable and condensed chromatin organization that represses eukaryotic transcription. Here we report that DNA methylation at the OC gene locus is associated with the condensed chromatin structure found in cells not expressing OC. In addition, we find that reduced CpG methylation of the OC gene accompanies active transcription in ROS 17/2.8 rat osteosarcoma cells. Interestingly, during differentiation of primary diploid rat osteoblasts in culture, as the OC gene becomes increasingly expressed, CpG methylation of the OC promoter is significantly reduced. Inhibition of OC transcription does not occur by a direct mechanism because in vitro methylated OC promoter DNA is still recognized by the key regulators Runx/Cbfa and the vitamin D receptor complex. Furthermore, CpG methylation affects neither basal nor vitamin D-enhanced OC promoter activity in transient expression experiments. Together, our results indicate that DNA methylation may contribute indirectly to OC transcriptional control in osteoblasts by maintaining a highly condensed and repressed chromatin structure.

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KW - Osteocalcin

KW - Transcription

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