Table 2.
List of histone chaperones, histone modifiers or histone readers localizing within PML NBs. Only proteins with known localization in PML NBs are listed, those that interact with PML, but whose localization in PML NBs has not yet been proven, have been omitted. Presence of validated SUMOylation sites or SIM motifs is indicated, putative sites/motifs identified by bioinformatic analysis or in SUMO screens are not shown. Positions refers to human proteins unless stated otherwise. While HP1 has been shown to be SUMOylated (236), it remains to be determined whether this SUMOylation controls its localization in PML NBs. The function related to the localization in PML NBs is also depicted. n.d. : non determined. hMSCs : human mesenchymal stem cells. MARs : Matrix attachment regions
| Protein | Protein function | SUMO | SIM | Recruitment | Function related to localization in PML NBs | References for PML NB localization | References for SUMO/SIM |
|---|---|---|---|---|---|---|---|
| ATRX | H3.3 histone chaperone | n.d. | n.d. | Constitutive, DAXX-dependent | Heterochromatin establishment | (82–83) | - |
| CBP | Histone acetyltransferase | n.d. | n.d. | Constitutive | Transcriptional regulation via p53 acetylation | (53,72–73) | - |
| DAXX | H3.3 histone chaperone | Multiple lysine residues | SIM1 IIVL (aa 7-10) and SIM2 IIVLSDSD (aa 733–740) | Constitutive | Transcriptional regulation, heterochromatin establishment, H3.3 recruitment in PML NBs, H3.3-dependent chromatin assembly | (25,61) | (118) |
| DEK | H3.3 histone chaperone | n.d. | AKRE (aa 260–263) (not validated by mutation) | Constitutive (hMSCs) | Maintenance of an H3.3 soluble pool available for recruitment in PML NBs | (101) | (101) |
| H3.3 | Histone H3 variant found in transcriptionally active regions and specific heterochromatic regions | n.d. | n.d. | Constitutive as well in senescence, DAXX-dependent | H3.3 soluble pool available for triage between histone chaperones | (84–85) | - |
| HDAC7 | Class IIA histone deacetylase | n.d. | n.d. | Constitutive in a subset of PML NBs, increased upon TNF-α | Transcriptional regulation (sequestration in PML NBs to relieve gene repression) | (108) | - |
| HIRA complex | H3.3 histone chaperone complex composed of HIRA, UBN1, CABIN1 and transiently ASF1A | n.d. | n.d. | Stress-induced (senescence, IFN, viral infection) | H3.3-dependent chromatin assembly in transcriptionally active regions, sequestration mechanism ? | (78,95–100) | - |
| HP1 | Heterochromatin protein 1 | K84 + alternative usage of various lysines residues | n.d. | Constitutive as well as in senescence | Heterochromatin establishment, in particular at cell-cycle genes during senescence | (75–78) | (236) |
| MOZ (KAT6A) | Histone acetyltransferase | n.d. | n.d. | Stress-induced (DNA damage, senescence) | Transcriptional regulation via p53 acetylation | (112) | - |
| SATB1 | Chromatin organizer by anchoring of MARs to the nuclear matrix, transcriptional regulator | K744 | n.d. | Constitutive in a subset of PML NBs, SUMO-dependent | Transcriptional regulation in immune cells, regulation of SATB1 levels by caspase-induced cleavage | (143,182) | (182) |
| SETDB1 | Histone H3K9 trimethyltransferase | n.d. | IIEI (aa 125–129) | Constitutive | H3K9me3 heterochromatin establishment at specific loci (such as Id2 gene) + maintenance of PML NBs | (102) | (122) |
| SIRT1 | NAD-dependent histone deacetylase | n.d. | n.d. | Stress-induced (PML-IV overexpression, senescence) | Deacetylation of p53 leading to repression of p53-mediated transactivation | (109) | - |
| TET2 | Oxidation of 5mC to promote DNA demethylation | n.d. | n.d. | Chemotherapy-induced, dependent on PML C-Terminus | Chemotherapy-induced demethylation of specific genes | (113) | - |
| TIP60 (KAT5) | Histone acetyltransferase | K430 and K451 | n.d. | UV-induced, SUMO-dependent, PML3-dependent | UV-induced DNA damage response (p53 recruitment in PML NBs and stabilization), SUMOylation promotes HAT activity, regulation of KAT5A stability | (110–111) | (110) |