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

Fernando Cruzat, Berta Henriquez, Alejandro Villagra, Matias Hepp, Jane B. Lian, Andre J. Van Wijnen, Janet L. Stein, Anthony N. Imbalzano, Gary S. Stein, Martin Montecino

Resultado de la investigación: Article

19 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)7287-7295
Número de páginas9
PublicaciónBiochemistry
Volumen48
N.º30
DOI
EstadoPublished - 4 ago 2009

Huella dactilar

Acetylation
Transcription
Chromatin Assembly and Disassembly
Histones
Chromatin
Hypersensitivity
Bone
Genes
Bone and Bones
Osteoblasts
Protein Isoforms
RNA Polymerase II
Deoxyribonuclease I
Genetic Promoter Regions
Transcription Factors

ASJC Scopus subject areas

  • Biochemistry

Citar esto

Cruzat, Fernando ; Henriquez, Berta ; Villagra, Alejandro ; Hepp, Matias ; Lian, Jane B. ; Van Wijnen, Andre J. ; Stein, Janet L. ; Imbalzano, Anthony N. ; Stein, Gary S. ; Montecino, Martin. / 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. En: Biochemistry. 2009 ; Vol. 48, N.º 30. pp. 7287-7295.
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abstract = "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.",
author = "Fernando Cruzat and Berta Henriquez and Alejandro Villagra and Matias Hepp and Lian, {Jane B.} and {Van Wijnen}, {Andre J.} and Stein, {Janet L.} and Imbalzano, {Anthony N.} and Stein, {Gary S.} and Martin Montecino",
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Cruzat, F, Henriquez, B, Villagra, A, Hepp, M, Lian, JB, Van Wijnen, AJ, Stein, JL, Imbalzano, AN, Stein, GS & Montecino, M 2009, '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', Biochemistry, vol. 48, n.º 30, pp. 7287-7295. https://doi.org/10.1021/bi9004792

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. / Cruzat, Fernando; Henriquez, Berta; Villagra, Alejandro; Hepp, Matias; Lian, Jane B.; Van Wijnen, Andre J.; Stein, Janet L.; Imbalzano, Anthony N.; Stein, Gary S.; Montecino, Martin.

En: Biochemistry, Vol. 48, N.º 30, 04.08.2009, p. 7287-7295.

Resultado de la investigación: Article

TY - JOUR

T1 - 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

AU - Cruzat, Fernando

AU - Henriquez, Berta

AU - Villagra, Alejandro

AU - Hepp, Matias

AU - Lian, Jane B.

AU - Van Wijnen, Andre J.

AU - Stein, Janet L.

AU - Imbalzano, Anthony N.

AU - Stein, Gary S.

AU - Montecino, Martin

PY - 2009/8/4

Y1 - 2009/8/4

N2 - 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.

AB - 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.

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