Molecular Mechanism And Effect Of Homeobox Gene HOXB6 On SOX9 Expression

The transcription factor named homeobox B6(HOXB6)is a member of the homeobox(HOX)gene family.As an important transcription factor,HOXB6 affects the phenotype of the body by regulating many target genes which are involved in many physiological activities.However,the research of HOXB6 focuses on its role in differentiation and development of embryonic.It is not known whether HOXB6 acts as transcrition factor in regulation the developmental genes.As a member of the SOX gene superfamily,the sex determination region Y box 9(SOX9)is critical in animal sex determination and differentiation,and it is involved in embryonic development and formation of various tissues and organs.In addition,SOX9 plays an important role in tissue damage repair and regeneration process.Many signaling pathways are involved in regulating SOX9,such as Notch,Wnt,TGFbeta and miRNA.Here,we investigate the role of HOXB6 on the expression of SOX9 and its underlying mechanism.Research results are as the following: 1.Downregulation HOXB6 enhanced the expression of SOX9Knockingdown of HOXB6 significantly promoted the expression of SOX9 in mRNA and protein levels by Realtime-PCR and Western Blot detection in HepG2 cells and HeLa cells.2.Upregulation HOXB6 repressed the expression of SOX9Overexpression of HOXB6 significantly inhibited the expression of SOX9 in mRNA and protein levels by Realtime-PCR and Western Blot detection in HepG2 cells and HeLa cells.3.HOXB6 repressed SOX9 promoter transactivityOverexpression of HOXB6 significantly inhibited SOX9 promoter transcription activity by double luciferase reporter system detection in HEK-293 T cells.4.HOXB6 specifically binds to the SOX9 gene promoterChromatin immunoprecipitation(ChIP)showed that HOXB6 binds specifically to the region from-736 to-609 upstream of the SOX9 transcription initiation site in HepG2 cells.