From: The influence of DNA sequence on epigenome-induced pathologies
Genes/Sequences affected | Genotype contribution | Known aberrant epitype/gene expression | Phenotype of epimutation or epigenetic change | Species | Supports/rejects hypothesis |
---|---|---|---|---|---|
A. Direct analysis of trans-generational inheritance | |||||
1. RYR1 ryanodine-receptor | Unknown | Cytosine hypermethylation/silenced | hyperthermia, core myopathies | human | Rejects |
2. MLH1 (Homolog of mismatch repair protein MutL) | Allele specific silencing | Cytosine hypermethylation/silenced | Colorectal or endometrial cancers | human | Weakly supports |
3. AGOUTI (paracrine signaling peptide) | Alleles with retrotransposon | Cytosine hypomethylation/activation | Yellow, obese | mouse | Supports |
4. AXIN1-FUSED | Alleles with retrotransposon | Cytosine hypomethylation, histone acetylation/activation | Axin-fused kinked tail | mouse | Supports |
5. CNR Colorless Non-Ripening | Native CpG rich region | Cytosine hypermethylation/silenced | Carotenoid synthesis | tomato | Rejects |
6. CYC – cycloidea (transcription factor) | Native CpG rich region and possible genotype difference | Cytosine hypermethylation/silenced | Floral morphology | Linaria vulgaris | Likely supports |
7. H3K4Me2 demethylase | None identified | Histone H3 lysine4 dimethylation retained causing gene activation | Germ line immortality | Caenorhabditis elegans | Likely rejects |
8. Quantitative epigenetic trait loci ( for example, many loci) | DNA DEMETHYLATION1 ddm1/ddm1 restored to DDM1/DDM1 | Cytosine re-methylation and re-silencing | Flowering time and plant height | Arabidopsis thaliana | Supports |
9. Reprogramming of 5Me C by dsRNA | siRNA, miRNA, piRNA, and other dsRNAs | Cytosine re-methylation and re-silencing | Complex, molecular, and developmental | Arabidopsis, mice | Supports |
10. Somatic cell nuclear transfer | Genome-wide | Cytosine re-methylation and histone modifications | Embryonic and fetal development | Mice, sheep, pigs, cows | Mostly supports |
B. Indirect analysis using sequence conservation and gene duplication | |||||
1. RRRRRYYYYY repeat throughout the genome | 10.5 bp repeats position most nucleosomes | N.M. | N.M. | Diverse animal species | Supports |
2a. Histone H2AZ in >1,000 nucleosomes | 10 bp repeat of G + C and A + T rich dinucleotides | Histone H2AZ variant positioning | Potentiated for expression. N.M. | Yeast, human, Arabidopsis | Supports |
2b. H2AZ in FLC, MAF4, MAF5 | Subfamily of three recently duplicated MADS box genes | Bimodal distribution of H2AZ enriched nucleosomes/activated | Altered flowering time and gene expression | Arabidopsis | Supports |
3. Histone CenH3 in ~100,000 nucleosomes | 10 bp repeat of AA or TT dinucleotides | Histone CenH3 variant positioning | Essential for chromosomal segregation. N.M. | maize | Supports |
4. Blood plasminogen genes (PMGs) | Cytosine methylation in 208 bp region upstream of four PMG genes | N.M. | Demethylation activates four linked PMG alleles genes in liver. Methylation silences in other organs. | human | Supports |
5. 1600 segmental duplications | Duplicated gene sequences | Several different histone side chain modifications | Duplicate alleles generally silenced relative to active parental allele. N.M. | human | Rejects |
6. HoxD cluster | Five gene duplicated HOXD genes | Modestly conserved nucleosomal and H3K4Me2 patterns | N.M. | human | Supports |
7. DNA loops and microsatellites | Concatenated DNA loops and trans-chromosomal contacts | Binding by HMG box proteins to control gene expression | N.M. | mammals | Modestly supports |