Examinando por Autor "Gordon, Jonathan A.R."

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    Epigenetic pathways regulating bone homeostasis:Potential targeting for intervention of skeletal disorders
    (Current Medicine Group LLC 1, 2014) Gordon, Jonathan A.R.; Montecino, Martin A.; Aqeilan, Rami I.; Stein, Janet L.; Stein, Gary S.; Lian, Jane B.
    Epigenetic regulation utilizes different mechanisms to convey heritable traits to progeny cells that are independent of DNA sequence, including DNA silencing, posttranslational modifications of histone proteins, and the posttranscriptional modulation of RNA transcript levels by noncoding RNAs.Although long non-coding RNAs have recently emerged as important regulators of gene imprinting, their functions during osteogenesis are as yet unexplored.In contrast, microRNAs (miRNAs) are well characterized for their control of osteogenic and osteoclastic pathways; thus, further defining how gene regulatory networks essential for skeleton functions are coordinated and finely tuned through the activities of miRNAs.Roles of miRNAs are constantly expanding as new studies uncover associations with skeletal disorders.The distinct functions of epigenetic regulators and evidence for integrating their activities to control normal bone gene expression and bone disease will be presented.In addition, potential for using “signature miRNAs” to identify, manage, and therapeutically treat osteosarcoma will be discussed in this review. © Springer Science+Business Media New York 2014.
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    Epigenetic regulators controlling osteogenic lineage commitment and bone formation
    (Elsevier Inc., 2024) Dashti, Parisa; Lewallen, Eric A.; Gordon, Jonathan A.R.; Montecino, Martin A.; Davie, James R.; Davie J.R.; Stein, Gary S.; van Leeuwen, Johannes P.T.M.; van der Eerden, Bram C.J.; van Wijnen, Andre J.
    Bone formation and homeostasis are controlled by environmental factors and endocrine regulatory cues that initiate intracellular signaling pathways capable of modulating gene expression in the nucleus. Bone-related gene expression is controlled by nucleosome-based chromatin architecture that limits the accessibility of lineagespecific gene regulatory DNA sequences and sequence-specific transcription factors. From a developmental perspective, bone-specific gene expression must be suppressed during the early stages of embryogenesis to prevent the premature mineralization of skeletal elements during fetal growth in utero. Hence, bone formation is initially inhibited by gene suppressive epigenetic regulators, while other epigenetic regulators actively support osteoblast differentiation. Prominent epigenetic regulators that stimulate or attenuate osteogenesis include lysine methyl transferases (e.g., EZH2, SMYD2, SUV420H2), lysine deacetylases (e.g., HDAC1, HDAC3, HDAC4, HDAC7, SIRT1, SIRT3), arginine methyl transferases (e.g., PRMT1, PRMT4/CARM1, PRMT5), dioxygenases (e.g., TET2), bromodomain proteins (e.g., BRD2, BRD4) and chromodomain proteins (e.g., CBX1, CBX2, CBX5). Thisnarrative review provides a broad overview of the covalent modifications of DNA and histone proteins that involve hundreds of enzymes that add, read, or delete these epigenetic modifications that are relevant for selfrenewal and differentiation of mesenchymal stem cells, skeletal stem cells and osteoblasts during osteogenesis