The role of SATB2 in skeletogenesis and human disease

Since the discovery of SATB2 (special AT-rich sequence binding protein 2) a decade ago, its pivotal roles in development and tissue regeneration have emerged, particularly in craniofacial patterning and development, palate formation, and osteoblast differentiation and maturation. As a member of the special AT-rich binding proteins family that bind to nuclear matrix-attachment regions (MAR), it also displays functional versatility in central nervous development, especially corpus callosum and pons formation, cancer development and prognosis, as well as in immune regulation. At the molecular level, Satb2 gene expression appears to be tissue and stage-specific, and is regulated by several cytokines and growth factors, such as BMP2/4/7, insulin, CNTF, and LIF via ligand receptor signaling pathways. SATB2 mainly performs a twofold role as a transcription regulator by directly binding to AT-rich sequences in MARs to modulate chromatin remodeling, or through association with other transcription factors to modulate the cis-regulation elements and thus to regulate the expression of down-stream target genes and a wide range of biological processes. This contemporary review provides an exploration of the molecular characteristics and function of SATB2; including its expression and cytokine regulation, its involvement in human disease, and its potential roles in skeletogenesis.