Table 1.
Table showing the differences and similarities between the epigenetic reprogramming in mice and humans.
| Aspect | Mice | Humans |
|---|---|---|
| DNA Methylation | DNA methylation undergoes erasure during PGC development [163]. | DNA methylation is partially retained in mature gametes [10] |
| Histone-to-Protamine Transition | Histones are replaced by protamines during sperm maturation [164] | Histones are replaced by protamines during sperm maturation [164] |
| DNA Methylation Dynamics in Spermatogenesis | Re-establishment of DNA methylation during spermatogenesis [165] | Mechanisms of DNA methylation re-establishment not well explored |
| DNA Methylation Patterns in Oocytes | Unique bimodal pattern, predominantly in gene bodies (~40% methylation in oocytes) [1] | Higher average DNA methylation, predominantly in gene bodies (~54% methylation in oocytes) [166] |
| DNMT3L Expression | Essential for de-novo methylation in mouse oocytes [167] | Not expressed in human oocytes [168] |
| Retained Histones in Mature Sperm | Few nucleosomes are retained in mature sperm [169] | More nucleosomes are retained in mature sperm [170]. |
| DNA Methylation | Paternal protamines replaced by maternal histones, erasure of almost all paternal DNA methylation. Maternal DNA methylation largely preserved. | Global reprogramming of DNA methylation in the pre-implantation embryo, with substantial retention of maternal methylation. Less passive demethylation, possibly due to a more active role of DNMT1 [139]. |
| Zygotic Genome Activation (ZGA) | Major wave of ZGA at the 2-cell stage [171]. | Major wave of ZGA at the 8-cell stage [172]. |
| Chromatin Remodeling | Relaxed chromatin state in zygotes gradually resolved to a more canonical state by the blastocyst stage [173]. | Widespread open chromatin in pre-ZGA embryos, rapidly remodeled upon ZGA. Temporal regulation of chromatin accessibility dependent on transcriptional activation [174]. |
| Transcriptome | Differences in the transcriptome compared to humans. Similar transcription factors, but divergent regulation and networks [175]. | Similar transcription factors, but temporal regulation and networks can differ [175]. |
| De novo Methylation | Two phases of de novo methylation: first in the paternal genome in the zygote, second between the 4- and 8-cell stage coinciding with ZGA. Transient methylation of repeat elements [176]. | De novo methylation observed during pre-implantation development. Two phases: early-to-mid pronuclear stage in the paternal genome, and between the 4- and 8-cell stage coinciding with ZGA. Methylation of repeat elements, transient in subsequent developmental stages [177]. |
| Function of Repressive Chromatin | Repressive chromatin marks such as H3K27me3 play a role in reinforcing lineage specification in both mice and humans [178]. | The targeted gain of H3K27me3 is observed in the post-implantation embryo in mice, but the specific mechanisms and extent of H3K27me3’s function in humans are largely unexplored [178]. |
| Role of H3K9me2 | H3K9me2 is associated with methylated DNA in the post-implantation embryo in both mice and humans. However, its functional role is specialized and not required for the genome-wide gain of DNA methylation [179]. | H3K9me2’s specific functions in the post-implantation embryo in humans are not well understood, and its role may be different from mice. |
| Active Chromatin Marks | Active histone modifications like H3K4me3 and H3K27ac likely play a role in transcriptional regulation during lineage specification in both mice and humans [178]. | The specific requirements and effects of H3K4me3 and H3K27ac in establishing and reinforcing the transcriptional program during lineage specification may vary between mice and humans [178]. |
| Imprinted Gene Clusters | Conserved in methylation status, allelic expression, and synteny [17] | Conserved in methylation status, allelic expression, and synteny, with several exceptions [17] |
| Number of Imprinted Genes | ~151 [180] | 50–90 [181] |
| Identification Methods | Sequencing approaches over SNPs, genomic imbalances [181] | Sequencing approaches over SNPs, genomic imbalances [181] |
| Regulatory Complexity | Imprinted gene expression and methylation may be more widespread and variable [180] | Imprinted gene expression and methylation may be more widespread and variable than mice [182] |
| Maintenance of Imprints | Requires ZFP57 and other genetic factors during later stages [183] | Maintenance of imprints during human reprogramming is not well understood [178] |
| Placental Imprinting | Limited number of placental-specific imprinted gDMRs [184] | More than 1500 placental-specific imprinted gDMRs, mostly not conserved between species [185] |
| Imprinting mechanisms | DNA methylation, H3K27me3 (extra-embryonic lineages) [184] | DNA methylation, H3K27me3 (unknown if present) |