Identification of acetyltransferase genes (HAT1 and KAT8) regulating HBV replication by RNAi screening

Hui Wang; KeHui Liu; Bernard A M Fang; HaiQing Wu; FengDi Li; XiaoGang Xiang; WeiLiang Tang; GangDe Zhao; LanYi Lin; Shisan Bao; Qing Xie

doi:10.1186/s13578-015-0059-1

Identification of acetyltransferase genes (HAT1 and KAT8) regulating HBV replication by RNAi screening

Cell Biosci. 2015 Dec 4:5:66. doi: 10.1186/s13578-015-0059-1. eCollection 2015.

Authors

Hui Wang^#¹, KeHui Liu^#¹, Bernard A M Fang^#^{2

3}, HaiQing Wu^{1

4}, FengDi Li¹, XiaoGang Xiang¹, WeiLiang Tang¹, GangDe Zhao¹, LanYi Lin¹, Shisan Bao^{1

2}, Qing Xie¹

Affiliations

¹ Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Discipline of Pathology, School of Medical Sciences and The Bosch Institute, Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006 Australia.
³ Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, NSW 2006 Australia.
⁴ Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

^# Contributed equally.

Abstract

Background: The initiation of hepatitis B virus (HBV) replication involves the formation of covalently closed circular DNA (cccDNA) and its transcription into pregenomic RNA (pgRNA) in hepatocyte nuclei. The regulatory mechanism of HBV replication by acetyltransferase is thus far not well understood, but human acetyltransferase has been reported as being involved in the regulation of HBV replication.

Results: Depletion of KAT8 or HAT1 via RNA interference (RNAi) markedly down-regulated HBV-DNA and pgRNA levels in HepG2.2.15 cells, with KAT8 knockdown reducing both HBsAg and HBeAg more than HAT1 knockdown. Consistent with these observations, HBV replication regulators hepatocyte nuclear factor-4-α (HNF4α) and peroxisome proliferator-activated receptor gamma coactivator- (PPARGC-) 1-α were decreased following knockdown of HAT1 or KAT8.

Conclusions: These data suggest that KAT8 or HAT1 regulate HBV replication and may be potential drug targets of anti-HBV therapy.

Keywords: KAT8, HAT1, HBV replication; RNAi screening; pgRNA.