| Positive Epigenetic Regulators of HIV Transcription |
|
|
|
| HATs (p300, CBP, P/CAF, hGCN5) |
Tat recruits transcriptional coactivators with HAT domains which are important in HIV activation. |
LTR-CAT reporter +/- Tat in HeLa, Jurkat, and 293 cell lines (integrated and non-integrated) |
[25-28] |
| H3K9ac, H3K14ac, H4K5ac, H34K8ac, H4K16ac, various HATs, total H3ac, total H4ac |
Study of TPA-induced LTR activation and recruitment of the listed marks/HATs over time via ChIP. |
LTR-CAT HeLa reporter (HL3T1, integrated) and U1 cell lines |
[29] |
| H3K36me2 |
Observed H3K36me2 in coding region upon TNF-α activation of LTR via ChIP. Implied positive regulator. |
OM-10.1 cell line |
[49] |
| H3K36me3 |
Observed in coding region via ChIP. Implied positive regulator. |
HLM107 cell line |
[56] |
| pBAF |
pBAF is important in Tat-mediated transcriptional activation of viral LTR. |
TZM-bl, productively infected PMBCs |
[111] |
| Negative Epigenetic Regulators of HIV Transcription |
|
|
|
| H3K4me3, H3K9me, LSD1 |
Decreased LSD1, H3K9me3, and H3K4me3 associated with increase in viral transcription. |
Human microglial cells and U1 cell line |
[48] |
| Total H3ac, Total H4ac, HDACs |
HDAC recruitment and loss of H3/H4 acetylation results in transcriptional repression. |
Various, including primary resting CD4+ T-cells from durably suppressed donors |
[32,33,35-37,44] |
| H3K79me2, DOT1L |
siRNA knockdown of H3K79 methyltransferase DOT1L and decreased H3K97me2 associated with increase in LTR-driven transcription. |
HeLa cells with integrated LTR-Luciferase reporter |
[51] |
| H3K27me3, PRC2 |
Decrease in H3K27 methylation via siRNA and small molecule targeting of PRC2 components results in increased viral transcription. |
Various Jurkat-derived latency reporter cell lines, primary T-cell models. |
[72-75] |
| PRC1 |
Observed PRC1 components at LTR during latency. Implied negative regulator. |
Jurkat-derived 2D10 reporter line, primary T-cell model |
[74] |
| H3K9me3, SUV39H1, HP1α/β/γ, CTIP2, HDAC1/2 |
Repressor CTIP2 recruits HDAC1/2, SUV39H1, and HP1 to the viral LTR, resulting in increased H3K9me3. |
Microglial, 293T, and HeLa lines with integrated or episomal LTR-Luciferase reporter, U1 cell line |
[40,95] |
| H3K9me3, SUV39H1, HP1γ |
siRNA knockdown of H3K9 methyltransferase SUV39H1 and reader HP1γ results in decreased H3K9me3 and increased H3ac and viral transcription. |
LTR-Luciferase reporter in HeLa (integrated and non-integrated/transient) |
[96] |
| H3K9me3, G9a |
siRNA and small molecule targeting of G9a results in loss of G9a and H3K9me3 at LTR and increased viral transcription. |
LTR-Luciferase reporter, Ach2, OM-10.1 cells lines |
[97] |
| HUSH Complex, SETDB1 |
Knockdown of HUSH complex (H3K9me3-mediated PEV) components results in viral reactivation. |
Jurkat LTR-Tat-GFP reporter, J-Lat models, and myeloid latency model |
[99] |
| Histone Chaperones (SUPT6H, FACT, CHD1, ASF1a, HIRA) |
Knockdown of various histone chaperones promotes viral reactivation. |
J-Lat models |
[115,117] |
| BAF |
Knockdown of BAF complex components promotes viral reactivation. |
J-Lat models and LTR-Luciferase reporter |
[110] |
