Table 2.
Modulation of lifespan by components and modifiers of chromatin¥
| Chromatin modification activity |
Protein (complex) |
Target histone and/or residue |
Chemical inhibitor |
Chemical activator |
Wild-type impact on health or lifespan |
Species |
|---|---|---|---|---|---|---|
| DNA methylation | dDNMT2 | 5-mC (?) | N/A | N/A | + | D. melanogaster |
| Histone Acetyltransferase | SAS2 | H4K16 | N/A | N/A | − | S. cerevisiae |
| GCN5 (SAGA complex) | H3, H3K14 | N/A | N/A | + | S. cerevisiae | |
| IKI3, SAS3 | H3K9, H3K14, H3K18 | spermidine | N/A | −/= | S. cerevisiae, D. melanogaster, C. elegans | |
| CBP | H4K5 | N/A | N/A | + | C. elegans | |
| Histone Deacetylase (Class I and II) | ? | Global effect | TrichostatinA, NaButyrate, PhenylButyrate, SAHA | N/A | + | D. melanogaster, C. elegans, M. musculus |
| RPD3 | H4K5, H4K12 | N/A | N/A | − | S. cerevisiae, D. melanogaster | |
| Histone Deacetylase (Class III) | SIR2(yeast), SIR2.1(worm), dSIR2 (fly) | H3K9, H3K14, H4K16 | Nicotinamide | N/A | + +/= +/= |
S. cerevisiae, D. melanogaster (?), C. elegans (?) |
| SIRT1 | H3K9, H3K14, H4K16 | Nicotinamide | SRT1720, SRT2104, SRT3025 | + | M. musculus | |
| SIRT6 | H3K9, H3K56 | Nicotinamide | N/A | + | M. musculus | |
| Histone Lysine methyltransferase | SET2 | H3K36 | N/A | N/A | +/− | S. cerevisiae |
| MET-1 | H3K36 (me3) | N/A | N/A | + | C. elegans | |
| SET-15 | ? | N/A | N/A | − | C. elegans | |
| SET-9, SET-26 | H3K4 (me1/2) | N/A | N/A | − | C. elegans | |
| SET1 | H3K4 (me3) | N/A | N/A | + | S. cerevisiae | |
| ASH-2, SET-2, WDR-5 (COMPASS complex) | H3K4 (me3) | N/A | N/A | − | C. elegans | |
| E(Z) (fly), MES-2 (worm) (Polycomb complex) | H3K27 | N/A | N/A | − | D. melanogaster, C. elegans | |
| Histone Lysine demethylase | RPH1 | H3K36 (me3) | N/A | N/A | − | S. cerevisiae |
| LSD-1 (T08D10.2 gene) | H3K4 (me2) | N/A | N/A | − | C. elegans | |
| RBR-2 (worm), LID (fly) | H3K4 (me3) | N/A | N/A | +/− +/= |
C. elegans, D. melanogaster | |
| JMJD-2 (worm), KDM4A(fly) | H3K9 | N/A | N/A | − −/= |
C. elegans, D. melanogaster | |
| UTX-1 | H3K27 | N/A | N/A | − | C. elegans | |
| Histone O-GlcNac regulation | OGT-1 | ? | N/A | N/A | + | C. elegans |
| OGA-1 | ? | N/A | N/A | −/= | C. elegans | |
| Histone monoubiquitinyl-transferase | RAD6, BRE1 (H2B monoubiquitination complex) | H2BK123 | N/A | N/A | + | S. cerevisiae |
| Nucleosome remodelers | ISW2 (ISWI complex) | N/A | N/A | N/A | − | S. cerevisiae, C. elegans |
| SWI/SNF | N/A | N/A | N/A | + | C. elegans | |
| CHD1 | N/A | N/A | N/A | − | S. cerevisiae | |
| LET-418 (worm), dMI2 (fly) (NurD complex) | N/A | N/A | N/A | − | C. elegans, D. melanogaster | |
| Histone chaperone | ASF1 | N/A | N/A | N/A | + | S. cerevisiae |
| HIR | N/A | N/A | N/A | − | S. cerevisiae | |
| Histone expression | H3/H4 | N/A | N/A | N/A | + | S. cerevisiae |
¥
see supplemental information S3 (table) for a fully referenced version of this table.
?
indicates where the parameter is unknown or unconfirmed.
N/A:not applicable
The “wild-type impact on health or lifespan” column indicates what role the protein or complexhas on lifespan in physiological conditions based on experimental knock-down, mutation or overexpression results(‘−‘ to indicate that they normally restrict health or lifespan, ‘+’ to indicate that they normally promote health or lifespan, ‘=’ when no clear impact on lifespan was reported).