Table 1

Summary of factors on HBV cccDNA and their functions

HBxPrevents the recruitment of transcriptional repressors or recruits transcription factors to cccDNA, thus activating transcription of HBV genes via epigenetic regulation; degrades SMC5/6, which binds cccDNA and inhibits its transcription31
HBcEnhances the formation of cccDNA via delivering the rcDNA to the nucleus from mature nucleocapsids41
CBP/p300Enhances the acetylation of cccDNA-bound histones25
PCAF/GCN5Enhances the acetylation of cccDNA-bound histones25
ATFEnhances cccDNA transcription25
CREBEnhances cccDNA transcription25
YY1Enhances cccDNA transcription25,35
STAT1/2Enhances cccDNA transcription25,35
Par14/17Enhances cccDNA transcription activation by binding HBx29
PRPF31Enhances cccDNA minichromosome formation or maintenance by interacting with HBx30
HDAC1Inhibits cccDNA transcription as a transcriptional suppressor34
SIRT1Inhibits cccDNA transcription as a chromatin modification enzyme34
IFI16Inhibits cccDNA transcription through enhancing recruitment of transcriptional suppressors and depressing transcriptional activators34
SMCHD1Suppresses cccDNA transcription34
PMLInhibits cccDNA transcription34
SMC5/6Inhibits cccDNA transcription31
SETDB1Inhibits transcription of cccDNA by SETDB1 histone methyltransferase32
HP1Inhibits cccDNA transcription32
PRMT1/5Mediates epigenetic suppression of the cccDNA minichromosome36
EZH2Inhibits cccDNA transcription34,37
DLEU2After co-recruitment to cccDNA with HBx, displaces EZH2 from the viral chromatin and boosts cccDNA transcription37
HAT1Modulates acetylation of histones on the cccDNA minichromosome38
HULCServes as a scaffold in the complex of HAT1/HULC/HBc; modulates acetylation of histones on the cccDNA minichromosome38
PCNAEnhances cccDNA formation from rcDNA39

HBx, hepatitis B X protein; HBc, hepatitis B core protein; CBP, CREB binding protein; PCAF, P300/CBP associated factors; GCN5, general control non-derepressible 5; ATF, artificial transcription factor; CREB, cAMP-response element binding protein; YY1, Yin Yang 1; STAT1/2, signal transducer and activator of transcription 1/2; Par14/17, parvulin 14/17; PRPF31, pre-messenger RNA processing factor 31; HDAC1, histone deacetylase 1; SIRT1, sirtuin 1; IFI16, interferon-inducible protein 16; SMCHD1, structural maintenance of chromosomes flexible hinge domain containing 1; PML, promyelocytic leukemia protein; SMC5/6, structural maintenance of chromosomes complex5/6; SETDB1, SET domain bifurcated histone lysine methyltransferase 1; HP1, heterochromatin-associated protein 1; PRMT1/5, protein arginine methyltransferase 1; EZH2, enhancer of zeste homolog 2; DLEU2, deleted in lymphocytic leukemia 2; HAT1, histone acetyltransferase 1; HULC, highly upregulated in liver cancer; PCNA, proliferating cell nuclear antigen.