title: Nuclear factor Y regulates ancient budgerigar hepadnavirus core promoter activity.
abstract: Endogenous viral elements (EVE) in animal genomes are the fossil records of ancient viruses and provide invaluable information on the origin and evolution of extant viruses. Extant hepadnaviruses include avihepadnaviruses of birds and orthohepadnaviruses of mammals. The core promoter (Cp) of hepadnaviruses is vital for viral gene expression and replication. We previously identified in the budgerigar genome two EVEs that contain the full-length genome of an ancient budgerigar hepadnavirus (eBHBV1 and eBHBV2). Here, we found eBHBV1 Cp and eBHBV2 Cp were active in several human and chicken cell lines. A region from nt -85 to -11 in eBHBV1 Cp was critical for the promoter activity. Bioinformatic analysis revealed a putative binding site of nuclear factor Y (NF-Y), a ubiquitous transcription factor, at nt -64 to -50 in eBHBV1 Cp. The NF-Y core binding site (ATTGG, nt -58 to -54) was essential for eBHBV1 Cp activity. The same results were obtained with eBHBV2 Cp and duck hepatitis B virus Cp. The subunit A of NF-Y (NF-YA) was recruited via the NF-Y core binding site to eBHBV1 Cp and upregulated the promoter activity. Finally, the NF-Y core binding site is conserved in the Cps of all the extant avihepadnaviruses but not of orthohepadnaviruses. Interestingly, a putative and functionally important NF-Y core binding site is located at nt -21 to -17 in the Cp of human hepatitis B virus. In conclusion, our findings have pinpointed an evolutionary conserved and functionally critical NF-Y binding element in the Cps of avihepadnaviruses.
authors: Key Laboratory of Medical Molecular Virology (Ministry of Health and Ministry of Education), Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200031, China.
authors: Zhongliang
authors: Z
authors: Shen
authors: Department of Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors: Yanfeng
authors: Y
authors: Liu
authors: Key Laboratory of Medical Molecular Virology (Ministry of Health and Ministry of Education), Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200031, China.
authors: Mengjun
authors: M
authors: Luo
authors: Key Laboratory of Medical Molecular Virology (Ministry of Health and Ministry of Education), Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200031, China.
authors: Wei
authors: W
authors: Wang
authors: Key Laboratory of Medical Molecular Virology (Ministry of Health and Ministry of Education), Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200031, China.
authors: Jing
authors: J
authors: Liu
authors: Key Laboratory of Medical Molecular Virology (Ministry of Health and Ministry of Education), Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200031, China.
authors: Wei
authors: W
authors: Liu
authors: Shanghai Keybiomed Technology Co., Ltd., Shanghai 201206, China. Electronic address: panshaokun@foxmail.com.
authors: Shaokun
authors: S
authors: Pan
authors: Key Laboratory of Medical Molecular Virology (Ministry of Health and Ministry of Education), Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200031, China. Electronic address: yhxie@fudan.edu.cn.
authors: Youhua
authors: Y
authors: Xie
mesh_terms: D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D001715:Bird Diseases / Q000821:virology; D023081:CCAAT-Binding Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002642:Chick Embryo; D002645:Chickens; D017124:Conserved Sequence; D004251:DNA Transposable Elements; D004279:DNA, Viral / Q000235:genetics* / Q000378:metabolism; D053476:Extinction, Biological; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D005580:Fossils; D016678:Genome; D057809:HEK293 Cells; D015613:Hepadnaviridae / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D018347:Hepadnaviridae Infections / Q000662:veterinary / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D046408:Melopsittacus; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D011485:Protein Binding
chemical_list: D023081:CCAAT-Binding Factor; D004251:DNA Transposable Elements; D004279:DNA, Viral; C402244:nuclear factor Y
keywords: Avihepadnavirus; Core promoter; Endogenous budgerigar hepadnavirus; NF-Y; Orthohepadnavirus