Fig 1.
Unique epigenetic features of the human placenta.
(A) DNA methylation dynamics during early human development. After fertilisation, the sperm and egg undergo a wave of hypomethylation, except at imprinted genes. Around implantation, the inner cell mass of the blastocyst, which develops into the epiblast, and the trophoblast, which develops into the placenta, undergo de novo methylation to differing extents. (B) Unique features of the placenta methylome arising as a result of the remethylation differences in A. B (i) Global hypomethylation [15, 16], (ii) polymorphic imprinting [17], (iii) PMDs [18, 19], (iv) trophoblast differentiation dynamics [13], (v) epigenetic regulation of HLA-G [20], (vi) tumour suppressor promoter methylation [21, 22], (vii) silencing of chemokines by a repressive histone mark, H3K27me3 [23], (viii) control of parturition by H3K27me3 in decidua [23], (ix) interindividual variation increases with gestation [24], (x) TERRA promoter hypomethylation [25], (xi) trophoblast DNA methylation is sensitive to oxygen concentration [14], (xii) hypomethylated retrotransposons used as alternative promoters [26, 27]. C, cytosine nucleotide; CpG, cytoside-guanine dinucleotide; CT, cytotrophoblast; CXCL9, C-X-C motif chemokine ligand 9; CXCL10, C-X-C motif chemokine ligand 9; EVT, extra-villous trophoblast; HLA-G, major histocompatibility complex, class I, G; H3K27me3, histone 3 Lysine 27 trimethylation; meC, methylated cytosine; PMD, partially methylated domain; SINE, short interspersed nuclear element; ST, syncytiotrophoblast; TERRA, telomere RNA.
Table 1.
Placenta epigenetics and environment.
Table 2.
Placenta epigenetics, disease, and fetal outcome.