Table 2 Roles of histone citrullination in physiological regulation
Function | Enzyme | Citrullination site | Cell type | Details |
|---|---|---|---|---|
Embryonic development | PAD1 | H4R3, H3R2, 8, 17 | Embryonic cells | Transactivation of the early embryo genome [80] |
Unknown | H3R2, 8, 17, H3R26, H4R3 | Zygotes | Upregulation of gene expression in early embryos [81] | |
PAD2 | H3R2, 8, 17, H3R26 | Ovine luminal epithelial | Gestation establishment [82] | |
Wound healing | PAD2 | H4R3 | Leukocyte in zebrafish | Novel signaling of regenerative growth [83] |
Senescence | Unknown | H1.0 | diploid fibroblasts | Regulation of aging associated with heterochromatinization [84] |
Reproductive function | PAD2 | H3R2, 8, 17 | Mammary gland epithelial | Regulation of lactation gene expression [85] |
PAD2 | H3R2, 8, 17 | Gonadotrope cell | Regulation of gonadotropin gene expression [86] | |
Chromatin activity | PAD4 | H1R54 | Embryonic stem cell | Changes in histone-DNA interaction and regulation of chromatin accessibility [87] |
PAD4 | H4R3 | Thymus | Promotion of chromatin decondensation and DNA fragmentation [56] | |
Unknown | H3R26 | Embryonic stem cell | SMARCAD1 regulates pluripotency by interacting with CitH3R26 [88] | |
Pluripotency | PAD4 | H1.2R53 | Stem cell line | Regulation of pluripotency and chromatin decondensation [5] |
Transcription | PAD4 | H3R2,8,17,26 H4R3, H2A | HL-60 | Antagonism against histone methylation [79] |
NET formation | PAD4 | H3 | Neutrophil | Antibacterial natural immunity [89] |
PAD2 | H3 | Neutrophil | PAD2 inhibition reduces NETosis and inflammatory cytokine [90] | |
PAD4 | H3 | Neutrophil | NET formation in the patient with COVID-19 [91] |