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The bone-specific Runx2-P1 promoter displays conserved three-dimensional chromatin structure with the syntenic Supt3h promoter.
Barutcu, A Rasim; Tai, Phillip W L; Wu, Hai; Gordon, Jonathan A R; Whitfield, Troy W; Dobson, Jason R; Imbalzano, Anthony N; Lian, Jane B; van Wijnen, André J; Stein, Janet L; Stein, Gary S.
Afiliação
  • Barutcu AR; Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
  • Tai PW; Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA Department of Biochemistry and Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405, USA.
  • Wu H; Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA Department of Biochemistry and Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405, USA.
  • Gordon JA; Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA Department of Biochemistry and Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405, USA.
  • Whitfield TW; Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
  • Dobson JR; Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
  • Imbalzano AN; Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
  • Lian JB; Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA Department of Biochemistry and Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405, USA.
  • van Wijnen AJ; Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
  • Stein JL; Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA Department of Biochemistry and Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405, USA.
  • Stein GS; Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA Department of Biochemistry and Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405, USA gary.stein@uvm.edu.
Nucleic Acids Res ; 42(16): 10360-72, 2014.
Article em En | MEDLINE | ID: mdl-25120271
ABSTRACT
Three-dimensional organization of chromatin is fundamental for transcriptional regulation. Tissue-specific transcriptional programs are orchestrated by transcription factors and epigenetic regulators. The RUNX2 transcription factor is required for differentiation of precursor cells into mature osteoblasts. Although organization and control of the bone-specific Runx2-P1 promoter have been studied extensively, long-range regulation has not been explored. In this study, we investigated higher-order organization of the Runx2-P1 promoter during osteoblast differentiation. Mining the ENCODE database revealed interactions between Runx2-P1 and Supt3h promoters in several non-mesenchymal human cell lines. Supt3h is a ubiquitously expressed gene located within the first intron of Runx2. These two genes show shared synteny across species from humans to sponges. Chromosome conformation capture analysis in the murine pre-osteoblastic MC3T3-E1 cell line revealed increased contact frequency between Runx2-P1 and Supt3h promoters during differentiation. This increase was accompanied by enhanced DNaseI hypersensitivity along with RUNX2 and CTCF binding at the Supt3h promoter. Furthermore, interplasmid-3C and luciferase reporter assays showed that the Supt3h promoter can modulate Runx2-P1 activity via direct association. Taken together, our data demonstrate physical proximity between Runx2-P1 and Supt3h promoters, consistent with their syntenic nature. Importantly, we identify the Supt3h promoter as a potential regulator of the bone-specific Runx2-P1 promoter.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article