Examinando por Autor "Stein, Janet L."

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    Epigenetic control of the bone-master Runx2 gene during osteoblast-lineage commitment by the histone demethylase JARID1B/KDM5B
    (American Society for Biochemistry and Molecular Biology Inc., 2015-12) Rojas, Adriana; Aguilar, Rodrigo; Henriquez, Berta; Lian, Jane B.; Stein, Janet L.; Stein, Gary S.; Van Wijnen, Andre J.; Van Zundert, Brigitte; Allende, Miguel L.; Montecino, Martin
    Transcription factor Runx2 controls bone development and osteoblast differentiation by regulating expression of a significant number of bone-related target genes. Here, we report that transcriptional activation and repression of the Runx2 gene via its osteoblast-specific P1 promoter (encoding mRNA for the Runx2/p57 isoform) is accompanied by selective deposition and elimination of histone marks during differentiation of mesenchymal cells to the osteogenic and myoblastic lineages. These epigenetic profiles are mediated by key components of the Trithorax/COMPASS-like and Polycomb group complexes together with histone arginine methylases like PRMT5 and lysine demethylases like JARID1B/KDM5B. Importantly, knockdown of the H3K4me2/3 demethylase JARID1B, but not of the demethylases UTX and NO66, prevents repression of the Runx2 P1 promoter during myogenic differentiation of mesenchymal cells. The epigenetically forced expression of Runx2/p57 and osteocalcin, a classical bone-related target gene, under myoblastic-differentiation is accompanied by enrichment of the H3K4me3 and H3K27ac marks at the Runx2 P1 promoter region. Our results identify JARID1B as a key component of a potent epigenetic switch that controls mesenchymal cell fate into myogenic and osteogenic lineages. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
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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.