Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus

Table 1 Canonical histone modifications implicated in TGS and TGA

Histone residue	Modification	Function	Writers	Erasers	Readers	Reviewed in
H3K4	Ac	Transcription activation				[228]
	me1 (enhancer sequences)me2/me3 (regulatory elements at the 5' end of active genes, and in poised genes)	Transcription activationTranscription activation, resolution of bivalency from poised genes	SET1 (tri)[229], SET7 (mono)[230], MLL[231], SMYD2[232]	LSD1 (mono and di)[233], JARID1A/KDM5A JARID1B/KDM5B (di and tri)[234]	CHD1[235], RAG2[236], TAF3[237], BPTF[238], BHC80[239], ING FAMILY[240], PYGO2[241]	[166,242]
H3T6	Phosphorylation	Transcription activation	PKC B		LSD1	[243]
H3K9	Acme1/me2me3 (non-genic regions, centromeric heterochromatin, satellite sequences, long terminal repeats)	Transcription activation, histone deposition	GCN5/PCAF[244]	SIRT6[245]	BRD4[246]	[247]
		Transcritional silencing, heterochromatin	SUV39H1/2[143], G9a[248], SETDB1[249]	JMJD1A/KDM3A[250], JMJD1B/KDM3B[251], JMJD1C/TRIP8, JMJD2A/KDM4A (B/C/D)[252]	HP1[253], EED 17406994), TDRD7[254], MPP8[255], UHRF1/2[256], GLP[248], CDY FAMILY[257]
H3K27	me1/me2/me3, heterochromatin and facultative heterochromatin	Transcritional silencing, heterochromatin, poised genes	EZH2, EZH1[258]	JMJD1A/KDM3A, JMJD1B/KDM3B, KDM6A/UTX, JMJD3/KDM68, JMJD3/KDM6B[259]	Cbx proteins[165], EED[260]	[166,261]
H3K36	Ac	Transcription activation	GCN5, PCAF[244]			[262]
	me1/me2 (in the body and 3' end of genes)me2/me3 (gene bodies)	Transcription elongation	NSD1, NSD2[263], SET2[264], SMYD2[232], MMSET[265]	ASH1[266], JHDM1[267], JHDM1A/KDM2A, JHDM1B/KDM2B[268]	ISW1B[269]
H4K20	me1 me2me3 (non-genic regions, centromeric heterochromatin, satellite sequences, long terminal repeats	Transcritional silencing, heterochromatin, repression of proinflammatory genes	PR-SET7/SET8[270] SUV420H1, SUV420H2[274]SUV420H2[274], SMYD5[275]	PHF8[271]PHF2[275]PHF2[275]	L3MBTL1[272]PHF20[276], L3MBTL1[277]NcoR[275]	[273]

H: Histone; K: Lysine residue; T: Threonine residue; me1: Monomethlyation; me2: Di-methylation; m3: Tri-methylation; SET1: Su(var)3-9, Enhacer of Zeste, Trithorax protein 1; SMYD2: SET and MYND domain containing protein 2; MLL: Mixed lienage leukemia protein; PKC-β: Protein kinase C beta; GCN5: general control nonderepressible-5; PCAF: P300/CBP associated factor; SUV39H1/2: Suppressor of variegation 3-9 homolog 1 or 2; SETDB1: SET domain bifurcated 1; NSD1: Nuclear receptor binding SET domain protein 1; MMSET: Multiple myeloma SET domain; PR-SET7/SET8: SET domain containing lysine methyltransferase 8; LSD1: Lysine (K) specific demethylase 1; JARID1A/KMT5: Jumonji/ARID 1 domain containing protein 1A; SIRT6: Sirtuin 6; JMJD1A: Jumonji domain containing protein 1A; ASH1: Absent small or homeotic like 1; JHMD1: Jmjc domain containing histone demethylase 1; PHF8: PHD finger protein 8; CHD1: Chromodomain-helicase-DNA binding protein 1; RAG2: Recombination activating gene 2; TAF3: TATA box binding protein (TBP)-associated factor; BPTF: Bromodomain and PHD finger containing transcription factor; ING Family: Inhibitor of growth; PYGO2: Pygopus family PHD finger 2; BRD4: Bromodomain-containing protein 4; TDRD7: Tudor domain-containing protein 7; MPP8: Methyl-H3K9-binding protein 8; UHRF1/2: Ubiquitin-like containing PHD and RING finger domains 1 or 2; CDY Family: Chromodomain Y chromosome family; GLP: G9a-like protein; ISWI1B: Imitation switch protein 1B; L3MBTL1: Lethal (3) malignant brain tumor-like protein 1; NcoR: Nuclear receptor coRepresor.

Table 2 Coordinates of transcription factor binding sites in the HIV-1 5’LTR

Name	Position1	Function	Cell type	Notes	Ref.
Nuc-0	About 40-200	Structural	Consistent across different cell types	Stable. Stability seems independent of transcription	[278]
AP-1/COUP-TF	About 103	Activation/Repression			[279]
c-myc/RBF-2 (USF1/2)	118-124	Repression/Activation	HeLa-CAT-CD4 and J-Lat J89 (Jurkat)	Binds the sequence CACTGAC in HIV promoter, but the canonical sequence is CACGTGAC	[280,281]
				Recruited by Sp1, can bind directly to the promoter to recruit HDAC1
				RBF-2 can potentially bind to the CTGAC of this motif.
AP-1/COUP-TF	About 135	Repression/Activation	Cell type variation	COUP-TF binds to the nuclear responsive element	[180,279]
NFAT	173	Activation	Consistent across different cell lines	NFAT consensus sequence TGGAAA maps on antisense strand	[282]
GRE-I	192-197	Repression/Activation	Cell type variation	GRE-like element AGAACA	[283-285]
AP-1	About 208			AP-1 recently found to be crucial for latency	[286]
YY1/RBF-2	About 336	Repression/Activation	Jurkat, HeLa	Putative E-box element RBEIII. Sequence overlaps YY1, RBF-2/TFII-I and AP-1 binding sites	[281,287,288]
NFAT/NF-kB	350	Activation/Repression	Consistent across different cell types	Two shared in-tandem binding sites for each transcription factor. NF-kB in the sense strand, NFAT in the antisense	[289-291]
COUP-TF/Sp1/CTIP-2	About 388	Activation/Repression	Microglial, Oligodendrocytes, T lymphocytes	COUP-TF synergises and interacts with SP1 to activate, while CTIP2 directly binds to SP1 and represses transcription	[279,292,293]
Nuc-1	450-610	Structural	Consistent across different cell types	This nucleosome is remodelled to induce HIV latency or transcriptional gene silencing	[278]
RBF-2/AP-4	435-440	Activation/Repression	HEK293T, Jurkat	Both bind the E-box element CAGCTG, which has been named RBEI	[288,294-296]
GRE-II	450-455	Activation/Repression	Cell type variation	GRE-like element TGTACT	[283-285]
LSF/YY1	about 440-483	Repression	HeLa	LSF recruits YY1. This interaction recruits HDCA1 to initiate repression	[281,297,298]
GRE-III	471-476	Repression/Activation	Cell type variation	GRE-like element AGACCA	[283-285]
COUP-TF/AP-1/SP3	About 485	Repression/Activation	Microglial	Synergises and interacts with SP3	[180,279]
RBF-2	About 576	Activation/Repression	Jurkat	Binds an atypical RBEIII element: ACTGCTGA	[288,294]
NFAT	618	Activation	Consistent across different cell lines	NFAT consensus sequence TGGAAA maps on sense strand	[291]

¹Genomic coordinates are based on the HBX2 numbering system. Nuc-0: Nucleosome 0; AP-1: Activator protein 1; COUP-TF: Chicken ovalbumin upstream transcription factor; c-myc: V-myc avian myelocytomatosis viral oncogene homolog; RBF-2: Ras-responsive binding factor 2; USF1/2: Upstream stimulatory factor 1 or 2; NFAT: Nuclear factor of activated T cells; GRE-I: Glucocorticoid responsive element I; YY1: Ying-yang 1; NF-κB: Nuclear factor kappa beta; Sp1: Specificity protein 1; CTIP-2: COUP-TF interacting protein 2; Nuc-1: Nucleosome 1; AP-4: Activator protein 4; GRE-II: Glucocorticoid responsive element II; Sp3: Specificity protein 3.