HPTMs | Models | Sites | Specific functions | References |
---|---|---|---|---|
Acetylation | Human brain | H3K9ac | H3K9ac is related to tau-related pathology and chromatin remodeling | [81] |
Human brain | H3K9ac, H3K27ac, H3K122ac | 1. H3K9ac and H3K27ac increase and H3K122ac reduction in AD 2. H3K9ac and H3K27ac are related to transcription, chromatin, and disease pathways | [20] | |
Human brain | H3K27ac | H3K27ac is associated with transcriptional variation at proximal genes | [19] | |
Human brain | H4K16ac | H4K16ac reduction in AD | [21] | |
Mice | H4K5ac, H4K12ac | App specifically regulates H4K5ac and H4K12ac and affects early memory-related genes in memory | [82] | |
Mice | H4 acetylation | 4-PBA treatment enhances the expression of genes related to induced learning and memory genes by increasing neuronal H4 acetylation | [83] | |
Human brain | H3 acetylation, H4 acetylation | H3 acetylation and H4 acetylation increase in high-pathological areas, with no significant change observed in low-pathological areas | [84] | |
Mice | H4 acetylation | APP/PS1 mice display a reduced H4 acetylation levels in response to a learning task | [85] | |
Mice | H3K9ac, H4K12ac | ACSS2 downregulation mediates a reduction in glutamate receptor expression through histone acetylation, which exacerbates synaptic plasticity impairment in AD | [22] | |
IPSC cell lines | H3K27ac | Knocking down P300/CBP reduces H3K27ac, inhibits the expression of genetic programs compensating for increased Aβ load, and leads to increased Aβ secretion | [23] | |
Drosophila | H4 acetylation | H4 acetylation may act as a defense against AD pathology-related insults | ||
Methylation | Human brain, Mice | H3K9me2 | Repressive H3K9me2 and euchromatic histone methyltransferases EHMT1 and EHMT2 are significantly elevated in the PFC | [31] |
Human brain, Mice | H3K4me3 | H3K4me3 and its catalytic enzymes are significantly elevated in the PFC in AD | [30] | |
Human brain | H4K20me2, H3K4me2, H3K27me3, H3K79me1, H3K79me2, H3K36me2, H4K20me3, H3K27me1, H3K56me1 | H4K20me2, H3K4me2, H3K27me3, and H3K79me1 increased, while H3K79me2, H3K36me2, H4K20me3, H3K27me1, and H3K56me1 decreased in AD | [20] | |
Mice | H3K4me3 | Histone methylation is actively regulated in the hippocampus and facilitates long-term memory formation | [28] | |
Mice | H3K4me2, H3K4me3 | KMT2B mediates hippocampal H3K4me2 and H3K4me3, which is critical for memory formation | [27] | |
Mice | H3K9me2 | Increased H3K9me2 levels in the cerebral cortex region and hippocampus region | [86] | |
Mice | H3K9me2 | NEP is significantly reduced in AD, and hypoxia may downregulate NEP by increasing H3K9me2 | [32] | |
Mice | H3K4me | A decrease in H3K4 methylation, resulting from KMT2A knockdown, partially recapitulates the pattern previously reported in CK-p25 mice | [29] | |
Human brain | H2BK108me, H4R55me | Reduced H2BK108 and H4R55 methylation in the frontal cortex region | [39] | |
Phosphorylation | Human brain | H4S47p | H4S47p increases in AD | [35] |
Human brain | H2AXS139p (γH2AX) | In the hippocampus region and cerebral cortex region, γH2AX significantly increased | [38] | |
Human brain | H3S10p | Activated H3S10p in AD is restricted to the neuronal cytoplasm | [36] | |
Human brain | H3 phosphorylation | H3 phosphorylation increases in AD | [37] | |
Ubiquitination | Human brain | H2BK120ub | H2BK120ub increases in the frontal cortex of AD | [39] |
Human neurons | H2A ubiquitination | Bmi1/Ring1 protein complex maintains the transcriptional inhibition of developmental genes through H2Aub | [41] | |
Mice | H2B ubiquitination | A deficiency of H2Bubi in the hippocampus prevents learning-induced increases in H3K4me3, gene transcription, synaptic plasticity, and memory formation | [40] |