Table 1. Class I HDAC complexes.
Seven representative class I HDAC complexes’ core components, interaction partners, biological functions, structural information, and complex-specific molecular tools are outlined.
| # | Complex name | Core components | Interaction partners | Biological functions | Available structures | Complex specific molecular tools (with references if available) |
|---|---|---|---|---|---|---|
| 1 | CoREST | HDAC1/2 | REST | Represses neuronal differentiation genes | EMD 10626–10630: CoREST complex alone and nucleosome-bound [28] | Rodin-A: HDAC1/2 inhibitor [58] |
| CoREST1/3 (RCOR1/3) | SNAG family transcription factors (SNAI1/2 GFI-1/1Betc) | Regulates stem cell fate and development [21–23,27] | SASDH45: CoREST complex SAXS [28] | corin: HDAC1/2-LSD1 dual inhibitor [25] | ||
| LSD1 (KDM1A) | HMG20A/B | Regulates epithelial/endothelial to mesenchymal transition [26,59] | PDBID 6VYP: LSD1-RCOR1 complex bound to nucleosome [38] | SNAG peptide: noncovalent LSD1 inhibitor [26] | ||
| CTBP1 | Mediates cell plasticity in cancer & vascular diseases [60,61] | tranylcypromine-derivatives: LSD1 covalent inhibitor | ||||
| GSE1 | tetrahydrofolate: LSD1 formaldehyde scavenger [62] | |||||
| ZNF217 | UM171: complex degrader [63,64] | |||||
| PHF21A | TALE-LSD1: LSD1 gene repressor [65] | |||||
| TERRA lncRNA | SP2509: LSD1 noncovalent inhibitor [66] | |||||
| HOTAIR lncRNA | domatinostat (4SC202): LSD1 & HDAC1 dual inhibitor and microtubule polymerization inhibitor [66,67] | |||||
| GATA2/3 | ||||||
| *More targets identified using BioID [68] | ||||||
| 2 | NuRD | HDAC1/2 | FOG1 | ATP-dependent chromatin remodeling | PDBID 5ICN: HDAC/MTA1 [69] | BPK-25: NuRD complex degrader [70] |
| MTA1/2/3 | BCL11A | Modulates developmental gene expression | PDBID 5FXY, 6G16: RBBP4/MTA1 [71] | p66α peptide: disrupts p66α MBD2 interaction [72] | ||
| RBBP4/7 | SALL4 | Maintains genome integrity | PDBID 7AO8, 7AO9, 7AOA: HDAC1/MTA1 dimer with MDB2 and with or without RBBP4 [50] | Biphenyl Calix[4]arenes: prevents CHD4-H3K9me3 interaction [73,74] | ||
| MBD2/3 | ZMYND8 | Cell cycle progression | EMD 22895: Low resolution model of NuRD complex [54] | |||
| CHD3/4/5 | ZNF187 | EMD-21382: MTA/HDAC/MBD complex [54] | ||||
| GATAD2A/B (p66α/β) | ATR (through CHD4) | PXD017378: CHD4 and CDK2AP2 XL-MS [52] | ||||
| CDK2AP1 | PWWP2A (replaces CHD MBD GATA and CDK2AP1) | PXD017244: RBBP7, MBD3, HDAC1, ZNF687, CHD4, and MTA1 XL-MS [52] | ||||
| 3 | MiDAC | HDAC1/2 | CCNA2 | Modulates developmental gene expression during embryogenesis | PDBID 4D6K & 2MWI: domain structures & stoichiometry [14] | n/a |
| MIDEAS | CDKN1A (p21) | Orchestrates chromosome alignment during mitosis | BMRB 25326: domain structures & stoichiometry [14] | |||
| DNTTIP1 | CDKN1B (p27) | PDBID 6Z2J & 6Z2K: dimeric and tetrameric complex [16] | ||||
| DNTT (TdT) | EMD 11041–11042: dimeric and tetrameric complex [16] | |||||
| 4 | MIER | HDAC 1/2 | CDYL1 | Maintenance of stemness | AF-Q8N108-F1 (predicted) | XY-07–104: Mier1/3 scaffold degrader [75] |
| MIER1/2/3 | REST [76] | Represses neuronal differentiation genes by REST association [76] | ||||
| EHMT2 [77]) | endothelial to mesenchymal transition [78] | |||||
| H2B [57] | ||||||
| SP1 [79] | ||||||
| WIZ [80] | ||||||
| 5 | RERE | HDAC1/2 | EHMT2 (G9a) | Regulates developmental gene expression | PDB 2YQK: SANT domain solution structure (unpublished) | miR-200b: regulates expression of RERE [81] |
| RERE | FAT1 [82]) | Epithelial-to-mesenchymal transition and mesenchymal cell proliferation [83] | AF-Q9P2R6-F1 (predicted) | miR-429: regulates expression of RERE [81] | ||
| ATN1 [84] | Retinoic acid signaling coactivation [17] | |||||
| 6 | Sin3 (A/B) | HDAC1/2 | BRMS1 | Regulates tissue development | PDBDEV_00000043: In silico model with XL-MS distance restraints – SIN3A/SAP30L/HDAC1 complex [85] | SID peptide: blocks MAD-SID interaction [86] |
| SAP30/30L | MAD1 | Cell cycle | PDB 2N2H: Solution structure of Sds3 in complex with Sin3A [87] | entinostat [88] | ||
| SIN3A/B | NANOG | Embryogenesis/pluripotency | PDB 2N1U: Structure of SAP30L [89] | tacedinaline [88] | ||
| SAP18 | ARID4A/B | DNA replication | PDB 2LD7: Solution structure of the mSin3A PAH3-SAP30 SID complex [90] | BML-210 [88] | ||
| SDS3 (SUDS3) | ING1 | |||||
| RBBP4/7 | SAP25 | |||||
| MXD1 | ||||||
| REST | ||||||
| HBP1 | ||||||
| 7 | SMRT | HDAC3/4/7 | TBL1XR1 | Lipid metabolism | PDBID 4A69: SMRT/HDAC3/IP4 [91] | Cpd-60: HDAC3 inhibitor that allows association with SMRT [48] |
| NCOR2 | TBL1Y | Macrophage polarization and inflammation | PDBID 2L5G: GPS2-SMRT [44] | Arsenic trioxide: MAPK-dependent SMRT phosphorylation causes complex dissociation [92] | ||
| GPS2 | SCF E3 ligase complex | Fibroblast cell cycle progression | PDBID 2XTC, 2XTD, 2XTE: TBL1 [44] | miRNA-100: silencing SMRT/NCOR2 gene [93] | ||
| TBL1X | E2-UBC5HC | Development | XY-07–090: NCOR1/HDAC3-degrader [75] | |||
| SUMOylated-NR1H2/NR5A2 | Circadian rhythms | |||||
| NR1H3 | ||||||
| ANKRD26 | ||||||
| ZBTB7A | ||||||
| AR | ||||||
| p53 | ||||||
| unliganded nuclear receptors (TR, RAR, RXR, PPAR) | ||||||
| orphan nuclear receptors | ||||||
| COUP-TFs | ||||||
| DAX1 | ||||||
| Rev-Erb |