Cellular transcription modulator SMARCE1 binds to HBV core promoter containing naturally occurring deletions and represses viral replication.
Suppression of hepatitis B virus (HBV) replication, a causative agent for chronic hepatitis, is an effective approach to controlling disease progression. Host factors have a significant effect on viral replication efficiency and need to be better characterized. We have reported association between clinical virus load and deletions in HBV viral promoter. We showed here that HBV genome with such deletions led to decreased replication compared with wild type virus. Consistently, the promoter with deletion showed lower activity. A cellular transcription regulator recognizing the promoter with deletion was revealed in gel shift assay and subsequently identified as SMARCE 1 through DNA-protein array assay. The ability of SMARCE 1 in modulating the replication efficiency of HBV was further demonstrated. Taken together, our studies show a direct dependence of HBV on a host factor to modulate its replication efficiency, and provided a new platform for molecular characterization of mechanisms of disease outcome as a result of binding of new transcription factors to rearranged promoter sequences.
Pan
Hong
H
School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
Niu
Dan Dan
DD
Feng
Huixing
H
Ng
Lisa F P
LF
Ren
Ee Chee
EC
Chen
Wei Ning
WN
D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism* / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism; D014779:Virus Replication
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C504738:SMARCE1 protein, human; D014157:Transcription Factors