Core binding factor (CBF) is required for Epstein-Barr virus EBNA3 proteins to regulate target gene expression
| Autor: | Paschos K, Quentin Bazot, Ho G, Ga, Parker, Lees J, Barton G, Mj, Allday |
|---|---|
| Přispěvatelé: | Wellcome Trust |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Biochemistry & Molecular Biology
DOWN-REGULATION 08 Information And Computing Sciences Science & Technology PROMOTER LYMPHOBLASTOID CELL-LINES 05 Environmental Sciences RUNX GENES 06 Biological Sciences TRANSCRIPTION FACTORS EBV B-CELLS J-KAPPA TUMOR-SUPPRESSOR 3C Life Sciences & Biomedicine Developmental Biology |
| Zdroj: | Europe PubMed Central |
| Popis: | ChIP-seq performed on lymphoblastoid cell lines (LCLs), expressing epitope-tagged EBNA3A, EBNA3B or EBNA3C from EBV-recombinants, revealed important principles of EBNA3 binding to chromatin. When combined with global chromatin looping data, EBNA3-bound loci were found to have a singular character, each directly associating with either EBNA3-repressed or EBNA3-activated genes, but not with both. EBNA3A and EBNA3C showed significant association with repressed and activated genes. Significant direct association for EBNA3B loci could only be shown with EBNA3B-repressed genes. A comparison of EBNA3 binding sites with known transcription factor binding sites in LCL GM12878 revealed substantial co-localization of EBNA3s with RUNX3-a protein induced by EBV during B cell transformation. The beta-subunit of core binding factor (CBFβ), that heterodimerizes with RUNX3, could co-immunoprecipitate robustly EBNA3B and EBNA3C, but only weakly EBNA3A. Depletion of either RUNX3 or CBFβ with lentivirus-delivered shRNA impaired epitope-tagged EBNA3B and EBNA3C binding at multiple regulated gene loci, indicating a requirement for CBF heterodimers in EBNA3 recruitment during target-gene regulation. ShRNA-mediated depletion of CBFβ in an EBNA3C-conditional LCL confirmed the role of CBF in the regulation of EBNA3C-induced and -repressed genes. These results reveal an important role for RUNX3/CBF during B cell transformation and EBV latency that was hitherto unexplored. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|