Table 1.
HAT enzymes and their roles in neurodegenerative disease (NDD).
| HAT family | Representative enzymes | Subcellular Localisation | Histone substrates | Examples of non-histone substrates | Identified eoles in brain | Identified involvement in *NDD |
|---|---|---|---|---|---|---|
| GNAT family (Roth et al., 2001; Yang, 2004; Kim et al., 2010; Wang Y. et al., 2014; Wang et al., 2020) | HAT1 | Nucleus/Cytoplasm | H4, H2A | HMG-N2/HMG17, AR, c-MYC, p53, and Ku70 | - | - |
| Gcn5 | Nucleus | H2B, H3 | Neural progenitor differentiation (Martínez-Cerdeño et al., 2012) | PD (Fan et al., 2020), *SCA7 (Chen et al., 2012) | ||
| PCAF | Nucleus | H3 | Regulates memories (Martínez-Cerdeño et al., 2012) | AD (Park et al., 2015), HD (Bodai et al., 2012) | ||
| HPA2 | Nucleus | H3, H4 | - | - | ||
| HPA3 | Nucleus | H4 | - | - | ||
| Elp3 | Nucleus/Cytoplasm | H3, H4 | Dendritic and axonal branching (Xu et al., 2000; Kim C. H. et al., 2012) | ALS (Simpson et al., 2009) | ||
| Elp1 | Nucleus | H3, H4 | - | |||
| MYST family (Roth et al., 2001; Yang, 2004; Kim et al., 2010; Wang Y. et al., 2014; Wang et al., 2020) | TIP60 | Nucleus/Cytoplasm | Embryonic neuronal development (Georgala et al., 2011; Kim C. H. et al., 2012) | AD (Müller et al., 2008), SCA1 (Gehrking et al., 2011) | ||
| MORF | Nucleus | H2A, H3, H4 | Adult neurogenesis (Thomas et al., 2000; Kueh et al., 2011) | AD (Li et al., 2021) | ||
| MOZ | Nucleus | H3, H4 | Regulation of neuronal progenitor cells & patterning genes (Katsumoto et al., 2006; Kueh et al., 2011; Perez-Campo et al., 2014; You et al., 2015) | AD (Li et al., 2021) | ||
| MOF | Nucleus/Mitochondria | H4 | AD (Li et al., 2021) | |||
| HBO1 | Nucleus | H4 | AD (Li et al., 2021) | |||
| Esa1 | Nucleus | H2AZ, H4 | - | - | ||
| Sas2 | Nucleus | H4 | - | - | ||
| Sas3 | Nucleus | H3 | - | - | ||
| p300/CREBBP (Roth et al., 2001; Yang, 2004; Kim et al., 2010; Wang Y. et al., 2014; Wang et al., 2020) | p300 | Nucleus/Cytoplasm | H2A, H2B, H3, H4 | HMG1, HMG-I(Y), p53, GATA-1, TCF, IF-2, ACTR (nuclear receptor coactivator), and SRC-1 | Neuronal tube development (Katsumoto et al., 2006; Kueh et al., 2011; Perez-Campo et al., 2014; You et al., 2015) and memory formation (Li et al., 2002; Korzus et al., 2004) | AD (Lu et al., 2014), PD (Kontopoulos et al., 2006), HD (Bodai et al., 2012) |
| CBP | Nucleus/Cytoplasm | H2A, H2B, H3, and H4 | AD (Caccamo et al., 2010), PD (Kontopoulos et al., 2006; Song et al., 2010), HD (Cong et al., 2005), ALS (Rouaux et al., 2003), and *SCA3 (Chai et al., 2002) |
AR, Androgen receptor; GATA-1, GATA-binding factor 1; HMG, high mobility group chromosomal protein; IF2, Initiation factor 2; SCA1, spinocerebellar ataxia type 1; SCA3, spinocerebellar ataxia type 3; SCA7, spinocerebellar ataxia type 7; SRC, Proto-oncogene tyrosine-protein kinase; and TCF, T-cell factor.
*
NDD: neurodegenerative disease.