Table 1 Correlation between rDNA methylation and embryonic development, aging, and diseases
From: The role of ribosomal DNA methylation in embryonic development, aging and diseases
Trait type | Trait | Tissue | Species | rDNA region | Methylation state changes | Other related changes | Reference | |
|---|---|---|---|---|---|---|---|---|
Development | Embryonic development | Sperm, germinal vesicle oocytes, metaphase II oocytes, zygote and blastocysts | Mouse | Promoter | Hypermethylation compared to adult tissues | Â | [24] | |
Sperm | Mouse | Promoter, transcribed region and IGS | Hypermethylation in aged sperm | (Peri)Centromeric minor and major satellite DNA, and interspersed LINE1 T repeats hypermethylation in aged sperm | [26] | |||
Rat | Transcribed region | Hypermethylation in aged sperm | - | [27] | ||||
Bull | Transcribed region | Hypermethylation in aged sperm | - | [26] | ||||
Marmoset | Transcribed region | Slight hypermethylation in aged sperm | - | [26] | ||||
Human | Promoter and transcribed region | Hypermethylation in aged sperm | - | [26] | ||||
Oocyte | Mouse | Promoter and transcribed region | Hypermethylation in aged oocytes | - | [28] | |||
Human | Promoter | Hypermethylation in oocytes from aging ovarian | Methylation changes between individual oocytes from the same donor are less than 5% in most samples | [28] | ||||
Zebrafish | Transcribed region | Hypermethylation | Germline amplification | [29] | ||||
Embryonic day 4.5 | Mouse | Promoter | Embryo methylation lower than extra-embryo | - | [24] | |||
Gonads and Liver cells of embryonic day 13.5 and 18.5 | Mouse | Promoter | Hypermethylation compared to primordial germ cells | - | [24] | |||
Liver cells of embryonic day 18.5 | Mouse | Promoter | Hypermethylation compared to embryonic day 13.5 | - | [24] | |||
Aging | Aging | Blood | Rat | Promoter | Hypermethylation | - | [14] | |
Human | Promoter | No significant change | - | [14] | ||||
Bone marrow cells | Mouse | Promoter | Hypermethylation | The number of rDNA copies increased and the levels of pre-rRNA transcripts decreased | [30] | |||
Fibroblasts | Human | Promoter | Hypermethylation | - | [31] | |||
Skeleton muscle | Mouse | Promoter | 15 sites were hypomethylated and 345 sites were hypermethylated | - | [32] | |||
Heart | Rat | Promoter | Hypermethylation | - | [14] | |||
Kidney | Rat | Promoter | Hypermethylation | - | [14] | |||
Liver | Rat | Promoter | Hypermethylation | - | [14] | |||
Transcribed region | Hypermethylation | - | [27] | |||||
Promoter and transcribed region | Hypermethylation | - | [33] | |||||
Human | Promoter and transcribed region | Hypermethylation | - | [33] | ||||
Diseases | Neurological diseases | Alzheimer’s disease (AD) | Cerebral cortex | Human | Promoter | Hypermethylation | An increase in overall rDNA content | [34] |
Mild cognitive impairment (MCI) | Cerebral cortex | Human | Promoter | Hypermethylation | An increase in overall rDNA content | [34] | ||
Schizophrenia (SCZ) | Neuronal and oligodendrocytes | Human | Transcribed region | No significant change | No significant change in rDNA copy number | [35] | ||
Autism spectrum disorders (ASD) | Brain | Human | Transcribed region | No significant change | No significant change in rDNA copy number | [35] | ||
Hematologic diseases | Myelodysplastic syndrome (MDS) | CD34 + cells | Human | Promoter | Hypermethylation | Decreased expression of rRNA, and alternation of ribosomal biogenesis | [36] | |
Genetic disorders | Werner’s syndrome (WS) | Fibroblasts | Human | Promoter, transcribed region and IGS | Hypermethylation | The steady-state levels of 28S rRNA remained constant over the life span of both normal and WS fibroblasts | [37] | |
Down syndrome (DS) | Whole blood | Human | Promoter | Hypermethylation | The number of rDNA copies increased | [38] | ||
Gender-specific cancers | Breast cancer | Breast | Human | Transcribed region | Hypermethylation | Increased methylation is associated with inhibition of estrogen receptor expression | [39] | |
Breast | Human | Promoter and transcribed region | Hypermethylation | Lower levels of rDNA methylation demonstrated significantly poorer rates of disease-free survival and overall survival | [40] | |||
Ovarian cancer | Ovary | Human | Transcribed region | Hypermethylation | Overexpression | [41] | ||
Cervical cancer | Cervical intraepithelial neoplasia tissue | Human | Promoter | Hypomethylation | Decondensation of rDNA, and rRNA overexpression | [42] | ||
Endometrial carcinoma | Endometrium | Human | Transcribed region | Hypermethylation | Morphological changes in the nucleoli, ac-companied by overexpression of rRNA | [43] | ||
Prostate cancer | Prostate | Human | Transcribed region | No significant change | rRNA overexpression | [44] | ||
Prostate | Human | IGS | Hypomethylation | Increased variation | [45] | |||
Other types of cancers | Oral squamous cell carcinoma (OSCC) | Oral | Human | Promoter and transcribed region | No significant change | Decreased expression of rRNA | [46] | |
Esophageal cancer | Esophagus | Human | IGS | Hypomethylation | Increased variation | [45] | ||
Hepatocellular carcinoma | Liver, cfDNA | Human | IGS | Hypomethylation | Increased variation | [45] | ||
Colorectal cancer | Colorectum, cfDNA | Human | IGS | Partial tumor samples show hypomethylation | - | [45] | ||
Lung cancer | Lung, cfDNA | Human | IGS | Partial tumor samples show hypomethylation | - | [45] | ||