Table 3.
Type of enzyme
|
Name of enzyme
|
PHD domain
|
Histone substrates
|
Function
|
Histone demethylation enzyme | KDM1B/LSD2 | PHD | H3K4me2 | Unknown[25] |
KDM2A | PHD | H3K36me2/me1 | Unknown[150] | |
KDM4A-C | Two PHD | Unknown | Unknown[155,197] | |
KDM5A | PHD1 | Unmethylated H3K4 histone tail | PHD1 finger by H3 N-terminal tail peptides stabilizes binding of the substrate to the catalytic finger and improves the catalytic efficiency of demethylation[198,199] | |
PHD2 | Unmodified H3K4 | Unknown[158] | ||
PHD3 | H3K4me3 | PHD3 finger can recruit substrate and it relates to demethylation propagation along nucleosomes via a positive-feedback regulatory mechanism[151,199] | ||
KDM5B | PHD1 | H3K4me0 | PHD1 finger recognizes the N-terminus of histone H3, provides an anchoring mechanism for KDM5B and PHD1-H3K4me0 is interaction is important for inhibition of migration[17] | |
PHD2 | Couldn’t bind to histone | Unknown[17] | ||
PHD3 | H3K4me3/H3K4me0 | PHD3 finger detects H3K4me3, anchors at chromatin and spreads the transcriptionally inactive state | ||
KDM5C | PHD1 | H3K4 | PHD1 finger stabilizes the substrate peptide and helps to position the H3K4 in the JmjC finger exactly[162] | |
PHF8(KDM7subfamily) | PHD1 | Suppressive marks on H3K9me2/me3 and H3K27me2/me3 and H4k20me2/me3 | PHD1 finger plays a significant role in PHF8 substrate recognition and helps to improve substrate affinity and specificity[164] | |
Histone methylation enzyme | KMT2A, KMT2B | PHD1 | Unknown | PHD1 finger is necessary for a context-dependent regulation of holocomplex formation and implicated in tumor suppression[143] |
PHD2 | Unknown | PHD2 finger shows the E3 ubiquitin ligase activity and involve in homo-dimerization[144,200]. Mutation in PHD2 will enhance transactivation ability and help to recruit target gene promoters | ||
PHD3 | H3K4me3/me2 | Unclear, one possibility is binding of H3K4me3 by PHD3 is necessary for the transcription-promoting effects of KMT2A/2B, another is to set a broad, methylated chromatin finger[145] | ||
PHD4 | Unknown | PHD4 finger mediates intramolecular interactions between the N-terminal and C-terminal fragments of KMT2A with PHD1, and improves its stability[143] | ||
KMT2C | Eight PHD fingers | Unknown | These fingers help KMT2C to recruit to its target genes correctly[30,146] | |
KMT2D | Seven PHD fingers | Unmodified histone H4 and asymmetrical H4R3me2 | These fingers are essential for methyltransferase activity of KMT2D and KMT2D-mediated differentiation[201] | |
KMT2E | PHD | H3K4me3 | PHD finger binds to H3K4me3 specially and facilitates the recruitment of KMT2E to active transcription chromatin regions[148,149,202] |
All current research on the regulation of writers and erasers by plant homeodomain domain. “Unknown” means that the corresponding literature was not mentioned. This table is sorted by types and subfamilies of enzymes. JmjC: Jumonji C; KMT: Histone lysine methyltransferase; PHD: Plant homeodomain.