Sp7/Osterix Is Restricted to Bone-Forming Vertebrates where It Acts as a Dlx Co-factor in Osteoblast Specification.
Sp7/Osterix Is Restricted to Bone-Forming Vertebrates where It Acts as a Dlx Co-factor in Osteoblast Specification.
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DOI：
10.1016/j.devcel.2016.04.002
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发表时间：
2016-05-09
影响因子：
11.8
通讯作者：
McMahon AP
中科院分区：
文献类型：
--
作者：
Hojo H;Ohba S;He X;Lai LP;McMahon AP
现存物种的骨形成仅限于脊椎动物物种。Sp 7/Osterix是骨分泌成骨细胞的关键转录决定因子。我们进行了Sp 7 ChIP-seq分析，鉴定了一大组预测的成骨细胞增强子，并在细胞培养和转基因小鼠试验中验证了其中的一个子集。SP家族成员通过其锌指结构域结合富含GC的靶序列。几条证据表明Sp 7的行为不同，从事成骨细胞的目标在Dlx含有监管复合物绑定到AT丰富的图案。Sp 7锌指结构域中的氨基酸差异降低了Sp 7对SP家族共有GC盒靶标的亲和力; Dlx 5结合映射到Sp 7的该结构域。这些数据支持一个模型，其中Dlx募集Sp 7成骨细胞增强子是Sp 7定向成骨细胞特化的基础。由于Sp 7样锌指变异体仅限于脊椎动物，因此Sp家族中Sp 7成员的出现可能与骨形成脊椎动物的进化密切相关。
Bone formation in extant species is restricted to vertebrate species. Sp7/Osterix is a key transcriptional determinant of bone-secreting osteoblasts. We performed Sp7 ChIP-seq 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 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. As 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 evolution of the bone forming vertebrates.