Genomic promoter occupancy of Runt-related transcription factor RUNX2 in osteosarcoma cells identifies genes involved in cell adhesion and motility

Margaretha Van Der Deen, Jacqueline Akech, David Lapointe, Sneha Gupta, Daniel W. Young, Martin A. Montecino, Mario Galindo, Jane B. Lian, Janet L. Stein, Gary S. Stein, Andre J. Van Wijnen

Resultado de la investigación: Article

54 Citas (Scopus)

Resumen

Runt-related transcription factors (RUNX1, RUNX2, and RUNX3) are key lineage-specific regulators of progenitor cell growth and differentiation but also function pathologically as cancer genes that contribute to tumorigenesis. RUNX2 attenuates growth and stimulates maturation of osteoblasts during bone formation but is also robustly expressed in a subset of osteosarcomas, as well as in metastatic breast and prostate tumors. To assess the biological function of RUNX2 in osteosarcoma cells, we examined human genomic promoter interactions for RUNX2 using chromatin immunoprecipitation (ChIP)-microarray analysis in SAOS-2 cells. Promoter binding of both RUNX2 and RNA polymerase II was compared with gene expression profiles of cells in which RUNX2 was depleted by RNA interference. Many RUNX2-bound loci (1550 of 2339 total) exhibit promoter occupancy by RNA polymerase II and contain the RUNX consensus motif 5′-((T/A/C)G(T/A/ C)GG(T/G). Gene ontology analysis indicates that RUNX2 controls components of multiple signaling pathways (e.g. WNT, TGFβ, TNFα, and interleukins), as well as genes linked to cell motility and adhesion (e.g. the focal adhesion-related genes FAK/PTK2 and TLN1). Our results reveal that siRNA depletion of RUNX2, PTK2, or TLN1 diminishes motility of U2OS osteosarcoma cells. Thus, RUNX2 binding to diverse gene loci may support the biological properties of osteosarcoma cells.

Idioma originalEnglish
Páginas (desde-hasta)4503-4517
Número de páginas15
PublicaciónJournal of Biological Chemistry
Volumen287
N.º7
DOI
EstadoPublished - 10 feb 2012

Huella dactilar

Cell adhesion
Osteosarcoma
Cell Adhesion
Cell Movement
Transcription Factors
Genes
RNA Polymerase II
Adhesion
Gene Ontology
Focal Adhesions
Chromatin Immunoprecipitation
Neoplasm Genes
Interleukins
Osteoblasts
Cell growth
Microarray Analysis
Microarrays
Growth
RNA Interference
Transcriptome

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Citar esto

Van Der Deen, Margaretha ; Akech, Jacqueline ; Lapointe, David ; Gupta, Sneha ; Young, Daniel W. ; Montecino, Martin A. ; Galindo, Mario ; Lian, Jane B. ; Stein, Janet L. ; Stein, Gary S. ; Van Wijnen, Andre J. / Genomic promoter occupancy of Runt-related transcription factor RUNX2 in osteosarcoma cells identifies genes involved in cell adhesion and motility. En: Journal of Biological Chemistry. 2012 ; Vol. 287, N.º 7. pp. 4503-4517.
@article{9208b99b20a64d92956f92d59a87ea75,
title = "Genomic promoter occupancy of Runt-related transcription factor RUNX2 in osteosarcoma cells identifies genes involved in cell adhesion and motility",
abstract = "Runt-related transcription factors (RUNX1, RUNX2, and RUNX3) are key lineage-specific regulators of progenitor cell growth and differentiation but also function pathologically as cancer genes that contribute to tumorigenesis. RUNX2 attenuates growth and stimulates maturation of osteoblasts during bone formation but is also robustly expressed in a subset of osteosarcomas, as well as in metastatic breast and prostate tumors. To assess the biological function of RUNX2 in osteosarcoma cells, we examined human genomic promoter interactions for RUNX2 using chromatin immunoprecipitation (ChIP)-microarray analysis in SAOS-2 cells. Promoter binding of both RUNX2 and RNA polymerase II was compared with gene expression profiles of cells in which RUNX2 was depleted by RNA interference. Many RUNX2-bound loci (1550 of 2339 total) exhibit promoter occupancy by RNA polymerase II and contain the RUNX consensus motif 5′-((T/A/C)G(T/A/ C)GG(T/G). Gene ontology analysis indicates that RUNX2 controls components of multiple signaling pathways (e.g. WNT, TGFβ, TNFα, and interleukins), as well as genes linked to cell motility and adhesion (e.g. the focal adhesion-related genes FAK/PTK2 and TLN1). Our results reveal that siRNA depletion of RUNX2, PTK2, or TLN1 diminishes motility of U2OS osteosarcoma cells. Thus, RUNX2 binding to diverse gene loci may support the biological properties of osteosarcoma cells.",
author = "{Van Der Deen}, Margaretha and Jacqueline Akech and David Lapointe and Sneha Gupta and Young, {Daniel W.} and Montecino, {Martin A.} and Mario Galindo and Lian, {Jane B.} and Stein, {Janet L.} and Stein, {Gary S.} and {Van Wijnen}, {Andre J.}",
year = "2012",
month = "2",
day = "10",
doi = "10.1074/jbc.M111.287771",
language = "English",
volume = "287",
pages = "4503--4517",
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Van Der Deen, M, Akech, J, Lapointe, D, Gupta, S, Young, DW, Montecino, MA, Galindo, M, Lian, JB, Stein, JL, Stein, GS & Van Wijnen, AJ 2012, 'Genomic promoter occupancy of Runt-related transcription factor RUNX2 in osteosarcoma cells identifies genes involved in cell adhesion and motility', Journal of Biological Chemistry, vol. 287, n.º 7, pp. 4503-4517. https://doi.org/10.1074/jbc.M111.287771

Genomic promoter occupancy of Runt-related transcription factor RUNX2 in osteosarcoma cells identifies genes involved in cell adhesion and motility. / Van Der Deen, Margaretha; Akech, Jacqueline; Lapointe, David; Gupta, Sneha; Young, Daniel W.; Montecino, Martin A.; Galindo, Mario; Lian, Jane B.; Stein, Janet L.; Stein, Gary S.; Van Wijnen, Andre J.

En: Journal of Biological Chemistry, Vol. 287, N.º 7, 10.02.2012, p. 4503-4517.

Resultado de la investigación: Article

TY - JOUR

T1 - Genomic promoter occupancy of Runt-related transcription factor RUNX2 in osteosarcoma cells identifies genes involved in cell adhesion and motility

AU - Van Der Deen, Margaretha

AU - Akech, Jacqueline

AU - Lapointe, David

AU - Gupta, Sneha

AU - Young, Daniel W.

AU - Montecino, Martin A.

AU - Galindo, Mario

AU - Lian, Jane B.

AU - Stein, Janet L.

AU - Stein, Gary S.

AU - Van Wijnen, Andre J.

PY - 2012/2/10

Y1 - 2012/2/10

N2 - Runt-related transcription factors (RUNX1, RUNX2, and RUNX3) are key lineage-specific regulators of progenitor cell growth and differentiation but also function pathologically as cancer genes that contribute to tumorigenesis. RUNX2 attenuates growth and stimulates maturation of osteoblasts during bone formation but is also robustly expressed in a subset of osteosarcomas, as well as in metastatic breast and prostate tumors. To assess the biological function of RUNX2 in osteosarcoma cells, we examined human genomic promoter interactions for RUNX2 using chromatin immunoprecipitation (ChIP)-microarray analysis in SAOS-2 cells. Promoter binding of both RUNX2 and RNA polymerase II was compared with gene expression profiles of cells in which RUNX2 was depleted by RNA interference. Many RUNX2-bound loci (1550 of 2339 total) exhibit promoter occupancy by RNA polymerase II and contain the RUNX consensus motif 5′-((T/A/C)G(T/A/ C)GG(T/G). Gene ontology analysis indicates that RUNX2 controls components of multiple signaling pathways (e.g. WNT, TGFβ, TNFα, and interleukins), as well as genes linked to cell motility and adhesion (e.g. the focal adhesion-related genes FAK/PTK2 and TLN1). Our results reveal that siRNA depletion of RUNX2, PTK2, or TLN1 diminishes motility of U2OS osteosarcoma cells. Thus, RUNX2 binding to diverse gene loci may support the biological properties of osteosarcoma cells.

AB - Runt-related transcription factors (RUNX1, RUNX2, and RUNX3) are key lineage-specific regulators of progenitor cell growth and differentiation but also function pathologically as cancer genes that contribute to tumorigenesis. RUNX2 attenuates growth and stimulates maturation of osteoblasts during bone formation but is also robustly expressed in a subset of osteosarcomas, as well as in metastatic breast and prostate tumors. To assess the biological function of RUNX2 in osteosarcoma cells, we examined human genomic promoter interactions for RUNX2 using chromatin immunoprecipitation (ChIP)-microarray analysis in SAOS-2 cells. Promoter binding of both RUNX2 and RNA polymerase II was compared with gene expression profiles of cells in which RUNX2 was depleted by RNA interference. Many RUNX2-bound loci (1550 of 2339 total) exhibit promoter occupancy by RNA polymerase II and contain the RUNX consensus motif 5′-((T/A/C)G(T/A/ C)GG(T/G). Gene ontology analysis indicates that RUNX2 controls components of multiple signaling pathways (e.g. WNT, TGFβ, TNFα, and interleukins), as well as genes linked to cell motility and adhesion (e.g. the focal adhesion-related genes FAK/PTK2 and TLN1). Our results reveal that siRNA depletion of RUNX2, PTK2, or TLN1 diminishes motility of U2OS osteosarcoma cells. Thus, RUNX2 binding to diverse gene loci may support the biological properties of osteosarcoma cells.

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