Epigenetic landscape during osteoblastogenesis defines a differentiation-dependent Runx2 promoter region

Phillip W.L. Tai, Hai Wu, Jonathan A.R. Gordon, Troy W. Whitfield, A. Rasim Barutcu, André J. van Wijnen, Jane B. Lian, Gary S. Stein, Janet L. Stein

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Runx2 is a developmentally regulated gene in vertebrates and is essential for bone formation and skeletal homeostasis. The induction of runx2-P1 isoform transcripts is a hallmark of early osteoblastogenesis. Although previous in vitro studies have defined a minimal Runx2-P1 promoter sequence with well-characterized functional elements, several lines of evidence suggest that transcription of the Runx2-P1 isoform relies on elements that extend beyond the previously defined P1 promoter boundaries. In this study, we examined Runx2-P1 transcriptional regulation in a cellular in vivo context during early osteoblastogenesis of MC3T3-E1 cultures and BMSCs induced towards the bone lineage by multi-layered analysis of the Runx2-P1 gene promoter using the following methodologies: 1) sequence homology among several mammalian species, 2) DNaseI hypersensitivity coupled with massively parallel sequencing (DNase-seq), and 3) chromatin immunoprecipitation of activating histone modifications coupled with massively parallel sequencing (ChIP-seq). These epigenetic features have allowed the demarcation of boundaries that redefine the minimal Runx2-P1 promoter to include a 336-bp sequence that mediates responsiveness to osteoblast differentiation. We also find that an additional level of control is contributed by a regulatory region in the 5'-UTR of Runx2-P1.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalGene
Volume550
Issue number1
DOIs
StatePublished - Oct 15 2014

Keywords

  • DNase hypersensitivity
  • Gene regulation
  • Histone modification
  • Osteoblast differentiation
  • Runx2-P1

ASJC Scopus subject areas

  • Genetics

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