Bioinformatics analysis of ZBED6 : interactome of Novel Transcription Factor ZBED6 in C2C12 Myoblasts

Sammanfattning: ZBED6 is a novel mammalian transcription factor that was recently identified and shown to act as a repressor of IGF2 transcription in skeletal muscle. Chromatin Immunoprecipitation (ChIP) sequence data in murine C2C12 myoblasts indicated that ZBED6 holds 2499 targeting sites. Whereas microarray data portrayed that ZBED6 differentially regulates almost 400 genes in C2C12 myoblasts. This data suggested that ZBED6 is targeting and regulating a vast array of genes, so there was a need to investigate system level knowledge of ZBED6. To elucidate the complete interactome of ZBED6 and particularly to build and visualize muscle-specific networks by using ChIP sequence and microarray data, Ingenuity Pathway Analysis (IPA) was employed. Networks of ZBED6-targeted genes suggested that ZBED6 mainly induces tissue development and is involved in development of cancer. These effects most likely involve the Wnt, human embryonic stem cell pluripotency and TGFẞ canonical pathways. Many of ZBED-targeted genes like IGF2, IGF1R, SRF, SMAD7, CDH2, CTNND2, PITX2, TRIO, WNT3a, WNT1, MSX1, PAX7, VEGFA, ACTN1, HEY1, SKI, E2F1, EP300, FGF9, MTOR, FGFRI, BMP7, and TGFẞ have established roles in skeletal muscle myogenesis. Whereas networks of ZBED6-regulated genes revealed that ZBED6 is mainly involved in organismal development and cell-to-cell interaction and signaling; and also engaged into hepatic fibrosis, clathrin-mediated endocytosis and tight junction signaling cascades. ZBED6-regulated genes including BMP4, DBP, CDH2, AGT, IGF1, IGF2, THBS1, PDGFRA, MPP2, AKT1, HGF, MET, FGF4, TGFẞ3, ACTN1, F2R, and VCAM1 have established roles in muscle proliferation, myogenesis and contraction. Our findings suggest that ZBED6 holds promise as a target to control and influence many cellular functions and canonical pathways and also controls many factors and cascades that are crucial for skeletal muscle myogenesis.