Examinando por Autor "Van Wijnen, A."
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Ítem Bookmarking the genome: Maintenance of epigenetic information(Elsevier, 2011-05) Zaidi, S.; Young, D.; Montecino, M.; Van Wijnen, A.; Stein, J.; Lian, J.; Stein, G.Mitotic inheritance of gene function is obligatory to sustain biological control. Emerging evidence suggests that epigenetic mechanisms are linked to transmission of cell fate, lineage commitment, and maintenance of cellular phenotype in progeny cells. Mechanisms of epigenetic memory include gene silencing by DNA methylation, transcriptional regulation by histone modifications, regulation of gene expression by noncoding small RNA molecules, and retention of regulatory machinery on target gene loci for activation and repression. We will focus on the regulatory implications of epigenetic memory for physiological control and for the onset and progression of disease. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.Ítem Genomic promoter occupancy of Runt-related transcription factor RUNX2 in osteosarcoma cells identifies genes involved in cell adhesion and motility(Elsevier, 2012-02) Van Der Deen, M.; Akech, J.; Lapointe, D.; Gupta, S.; Young, D.; Montecino, M.; Galindo, M.; Lian, J.; Stein, J.; Stein, G.; Van Wijnen, A.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.