Sp7/Osterix Is Restricted to Bone-Forming Vertebrates where It Acts as a Dlx Co-factor in Osteoblast Specification

Dev Cell. 2016 May 9;37(3):238-53. doi: 10.1016/j.devcel.2016.04.002. Epub 2016 Apr 28.


In extant species, bone formation is restricted to vertebrate species. Sp7/Osterix is a key transcriptional determinant of bone-secreting osteoblasts. We performed Sp7 chromatin immunoprecipitation sequencing analysis identifying a large set of predicted osteoblast enhancers and validated a subset of these in cell culture and transgenic mouse assays. Sp family members bind GC-rich target sequences through their zinc finger domain. Several lines of evidence suggest that Sp7 acts differently, engaging osteoblast targets in Dlx-containing regulatory complexes bound to AT-rich motifs. Amino acid differences in the Sp7 zinc finger domain reduce Sp7's affinity for the Sp family consensus GC-box target; Dlx5 binding maps to this domain of Sp7. The data support a model in which Dlx recruitment of Sp7 to osteoblast enhancers underlies Sp7-directed osteoblast specification. Because an Sp7-like zinc finger variant is restricted to vertebrates, the emergence of an Sp7 member within the Sp family was likely closely coupled to the evolution of bone-forming vertebrates.

Keywords: Dlx; Sp7/Osterix; bone; cis-regulation; evolution; osteoblast specification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AT Rich Sequence / genetics
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biological Evolution
  • DNA / metabolism
  • Enhancer Elements, Genetic / genetics
  • Gene Expression Regulation
  • Gene Knock-In Techniques
  • Genome
  • Homeodomain Proteins / metabolism*
  • Mice
  • Nucleotide Motifs / genetics
  • Osteoblasts / metabolism*
  • Osteogenesis*
  • Reproducibility of Results
  • Sp7 Transcription Factor
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Vertebrates / metabolism*


  • Homeodomain Proteins
  • Sp7 Transcription Factor
  • Sp7 protein, mouse
  • Transcription Factors
  • DNA