Genome-scale actions of master regulators directing skeletal development

The mammalian skeleton develops through two distinct modes of ossification: intramembranous ossification and endochondral ossification. During the process of skeletal development, SRY-box containing gene 9 (Sox9), runt-related transcription factor 2 (Runx2), and Sp7 work as master transcription factors (TFs) or transcriptional regulators, underlying cell fate specification of the two distinct populations: bone-forming osteoblasts and cartilage-forming chondrocytes. In the past two decades, core transcriptional circuits underlying skeletal development have been identified mainly through mouse genetics and biochemical approaches. Recently emerging next-generation sequencer (NGS)-based studies have provided genome-scale views on the gene regulatory landscape programmed by the master TFs/transcriptional regulators. With particular focus on Sox9, Runx2, and Sp7, this review aims to discuss the gene regulatory landscape in skeletal development, which has been identified by genome-scale data, and provide future perspectives in this field.