title: Mitotic Inheritance of mRNA Facilitates Translational Activation of the Osteogenic-Lineage Commitment Factor Runx2 in Progeny of Osteoblastic Cells.
abstract: Epigenetic mechanisms mediate the acquisition of specialized cellular phenotypes during tissue development, maintenance and repair. When phenotype-committed cells transit through mitosis, chromosomal condensation counteracts epigenetic activation of gene expression. Subsequent post-mitotic re-activation of transcription depends on epigenetic DNA and histone modifications, as well as other architecturally bound proteins that "bookmark" the genome. Osteogenic lineage commitment, differentiation and progenitor proliferation require the bone-related runt-related transcription factor Runx2. Here, we characterized a non-genomic mRNA mediated mechanism by which osteoblast precursors retain their phenotype during self-renewal. We show that osteoblasts produce maximal levels of Runx2 mRNA, but not protein, prior to mitotic cell division. Runx2 mRNA partitions symmetrically between daughter cells in a non-chromosomal tubulin-containing compartment. Subsequently, transcription-independent de novo synthesis of Runx2 protein in early G1 phase results in increased functional interactions of Runx2 with a representative osteoblast-specific target gene (osteocalcin/BGLAP2) in chromatin. Somatic transmission of Runx2 mRNAs in osteoblasts and osteosarcoma cells represents a versatile mechanism for translational rather than transcriptional induction of this principal gene regulator to maintain osteoblast phenotype identity after mitosis.
authors.affiliation: Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, Chile.|Department of Medical Technology, Faculty of Medicine, University of Chile, Santiago, Chile.|Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago, Chile.
authors.forename: Nelson
authors.initials: N
authors.lastname: Varela
authors.affiliation: Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, Chile.|Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago, Chile.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Aranguiz
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lizama
authors.affiliation: Center for Biomedical Research and FONDAP Center for Genome Regulation, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago, Chile.
authors.forename: Hugo
authors.initials: H
authors.lastname: Sepulveda
authors.affiliation: Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Antonelli
authors.affiliation: Departments of Orthopedic Surgery & Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Roman
authors.initials: R
authors.lastname: Thaler
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Moreno
authors.affiliation: Center for Biomedical Research and FONDAP Center for Genome Regulation, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago, Chile.
authors.forename: Martin
authors.initials: M
authors.lastname: Montecino
authors.affiliation: Department of Biochemistry, HSRF 326, Vermont Cancer Center for Basic and Translational Research, University of Vermont Medical School, Burlington, Vermont.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
authors.affiliation: Departments of Orthopedic Surgery & Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
authors.affiliation: Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, Chile.|Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago, Chile.
authors.forename: Mario
authors.initials: M
authors.lastname: Galindo
mesh_terms: D000818:Animals; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase; D005786:Gene Expression Regulation; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D007399:Interphase; D051379:Mice; D008938:Mitosis / Q000235:genetics*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D012333:RNA, Messenger; D015675:Osteocalcin