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Beschreibung

Nucleosome-remodeling factor subunit BPTF (UniProt A2A654 and E9Q6A7, also known as Bromodomain and PHD finger-containing transcription factor, Fetal Alz-50 clone 1 protein, Fetal Alzheimer antigen) is encoded by the Bptf (also known as Fac1, Falz) gene (Gene ID 207165) in murine species. BPTF, SNF2L and pRBAP46/48 are the three subunits of the nucleosome-remodelling factor NURF, an ISWI chromatin-remodeling complex that catalyzes ATP-dependent nucleosome sliding. BPTF mediates NURF target site specificity via interactions with transcription factors, histone variants and histone modifications on transcriptionally active genes. BPTF plays an important role in regulating nucleosome occupancy at nucleosome-free regions (NFRs) at sites occupied by the multivalent factors CTCF and cohesin via direct interaction with CTCF and the cohesin subunit SA2. In addition, BPTF also interacts with c-MYC and plays an essential role in its genomic distribution and biological activity. BPTF is necessary for the survival of c-MYC-overexpressing cells and for c-MYC-driven tumorigenesis in the mouse pancreas. BPTF knockdown leads to decreased c-MYC chromatin accessibility and significantly delays tumour development in pre-neoplastic pancreatic acinar cells. Consistently, BPTF expression in human tumours positively correlates with activation of c-MYC gene signatures.