Examinando por Autor "Stein, J."

Mostrando 1 - 3 de 3
  • Miniatura
    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.
  • Miniatura
    Ítem
    Ezh2-dependent H3K27me3 modification dynamically regulates vitamin D3-dependent epigenetic control of CYP24A1 gene expression in osteoblastic cells
    (Wiley-Liss Inc., 2020-01) Moena, D.; Nardocci, G.; Acevedo, E.; Lian, J.; Stein, G.; Stein, J.; Montecino, M.
    Epigenetic control is critical for the regulation of gene transcription in mammalian cells. Among the most important epigenetic mechanisms are those associated with posttranslational modifications of chromosomal histone proteins, which modulate chromatin structure and increased accessibility of promoter regulatory elements for competency to support transcription. A critical histone mark is trimethylation of histone H3 at lysine residue 27 (H3K27me3), which is mediated by Ezh2, the catalytic subunit of the polycomb group complex PRC2 to repress transcription. Treatment of cells with the active vitamin D metabolite 1,25(OH)2D3, results in transcriptional activation of the CYP24A1 gene, which encodes a 24-hydroxylase enzyme, that is, essential for physiological control of vitamin D3 levels. We report that the Ezh2-mediated deposition of H3K27me3 at the CYP24A1 gene promoter is a requisite regulatory component during transcriptional silencing of this gene in osteoblastic cells in the absence of 1,25(OH)2D3. 1,25(OH)2D3 dependent transcriptional activation of the CYP24A1 gene is accompanied by a rapid release of Ezh2 from the promoter, together with the binding of the H3K27me3-specific demethylase Utx/Kdm6a and thereby subsequent erasing of the H3K27me3 mark. Importantly, we find that these changes in H3K27me3 enrichment at the CYP24A1 gene promoter are highly dynamic, as this modification is rapidly reacquired following the withdrawal of 1,25(OH)2D3. © 2020 Wiley Periodicals, Inc.
  • Miniatura
    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.