Summary of factors on HBV cccDNA and their functions
| Name | Function | Reference |
|---|---|---|
| HBx | Prevents 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 transcription | 31 |
| HBc | Enhances the formation of cccDNA via delivering the rcDNA to the nucleus from mature nucleocapsids | 41 |
| CBP/p300 | Enhances the acetylation of cccDNA-bound histones | 25 |
| PCAF/GCN5 | Enhances the acetylation of cccDNA-bound histones | 25 |
| ATF | Enhances cccDNA transcription | 25 |
| CREB | Enhances cccDNA transcription | 25 |
| YY1 | Enhances cccDNA transcription | 25,35 |
| STAT1/2 | Enhances cccDNA transcription | 25,35 |
| Par14/17 | Enhances cccDNA transcription activation by binding HBx | 29 |
| PRPF31 | Enhances cccDNA minichromosome formation or maintenance by interacting with HBx | 30 |
| HDAC1 | Inhibits cccDNA transcription as a transcriptional suppressor | 34 |
| SIRT1 | Inhibits cccDNA transcription as a chromatin modification enzyme | 34 |
| IFI16 | Inhibits cccDNA transcription through enhancing recruitment of transcriptional suppressors and depressing transcriptional activators | 34 |
| SMCHD1 | Suppresses cccDNA transcription | 34 |
| PML | Inhibits cccDNA transcription | 34 |
| SMC5/6 | Inhibits cccDNA transcription | 31 |
| SETDB1 | Inhibits transcription of cccDNA by SETDB1 histone methyltransferase | 32 |
| HP1 | Inhibits cccDNA transcription | 32 |
| PRMT1/5 | Mediates epigenetic suppression of the cccDNA minichromosome | 36 |
| EZH2 | Inhibits cccDNA transcription | 34,37 |
| DLEU2 | After co-recruitment to cccDNA with HBx, displaces EZH2 from the viral chromatin and boosts cccDNA transcription | 37 |
| HAT1 | Modulates acetylation of histones on the cccDNA minichromosome | 38 |
| HULC | Serves as a scaffold in the complex of HAT1/HULC/HBc; modulates acetylation of histones on the cccDNA minichromosome | 38 |
| PCNA | Enhances cccDNA formation from rcDNA | 39 |
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.