Epigenetic landscape during osteoblastogenesis defines a differentiation-dependent Runx2 promoter region
AuthorsTai, Phillip W. L.
Gordon, Jonathan A.R.
Whitfield, Troy W.
Barutcu, Ahmet Rasim
Van Wijnen, Andre J.
Lian, Jane B.
Stein, Gary S.
Stein, Janet L.
Student AuthorsA. Rasim Barutcu
UMass Chan AffiliationsDepartment of Cell and Developmental Biology
Document TypeJournal Article
MetadataShow full item record
AbstractRunx2 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.
Gene. 2014 Oct 15;550(1):1-9. doi: 10.1016/j.gene.2014.05.044. Epub 2014 Jun 2. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/33482