Table 1.
Epigenetic changes observed during ageing¥
| Epigenetic mark |
Functional role |
Ageing paradigm |
Change in epigenetic mark with ageing |
Change observed in tissue/cells |
Detection method |
Species |
|---|---|---|---|---|---|---|
| 5-mC | Transcriptional repression (?) | Organismal (WS) | No global change | MSCs | RRBS | H. sapiens |
| Cellular (senescence) | Global decrease, local increases | Fibroblasts | Immunostaining, WGBS, chromatography | H. sapiens, M. musculus, M. auratus | ||
| Organismal | Minor global increase, local increasesand some local decreases | HSCs | RRBS, WGBS | M. musculus | ||
| Organismal | Local increases and some local decreases | Small intestine, Colon, Lung, Liver, Spleen, Brain, Blood, Kidney, Muscle | Pyrosequencing, MCAM, Beadchip arrays | H. sapiens, M. musculus | ||
| Organismal | Increase (LINEs), local decreases and rare local increases | Sperm | Pyrosequencing (LINEs), Beadchip arrays | H. sapiens | ||
| Organismal | No global change | Cortex | WGBS | M. musculus, H. sapiens | ||
| 5-hmC | Transcriptional activation (?) | Organismal | Minor increase (SINEs, LTRs) | Cerebellum | Immunostaining, Chemical tagging/ sequencing | M. musculus |
| Organismal | Minor global decrease | HSCs | HPLC-MS | M. musculus | ||
| mCH (where H represents A,C,T) | (?) | Organismal | Minor global decrease | Cortex | WGBS | H. sapiens, M. musculus |
| *Histone H2A | Core chromatin component | Cellular (senescence) | Decrease | Fibroblasts | Western blot | H. sapiens |
| Organismal (replicative lifespan) | Decrease | Yeast cells | Western blot | S. cerevisiae | ||
| *Histone H2B | Core chromatin component | Cellular (senescence) | Decrease | Fibroblasts | Western blot | H. sapiens |
| Organismal | Decrease | Muscle stem cells | Transcriptional profiling | M. musculus | ||
| *Histone H3 | Core chromatin component | Cellular (senescence) | Decrease | Epidermis, Fibroblasts | Immunostaining, Western blot, SILAC-MS | H. sapiens |
| Organismal (replicative lifespan) | Decrease, changes in occupancy | Yeast cells | Western blot, SILAC-MS | S. cerevisiae | ||
| Organismal | Decrease | Soma, Whole male flies, Muscle stem cells | Western blot (normalization to tubulin), Transcriptional profiling | C. elegans, D. melanogaster, M. musculus | ||
| Organismal | No Change | Head | Western blot (normalization to total protein or DNA) | D. melanogaster | ||
| H4 | Core chromatin component | Cellular (senescence) | Decrease | Fibroblasts | Western blot, SILAC-MS | H. sapiens |
| macroH2A | Component of heterochromatin | Cellular (senescence) | Increase | Fibroblasts | Immunostaining, Western blot | H. sapiens |
| Organismal | Increase | Lung, Liver | Immunostaining, Western blot | M. musculus | ||
| *HP1 | Component of heterochromatin | Organismal | Remodeling | Head, Gut, Fat cells | Immunostaining, ChIP-chip | D. melanogaster |
| HP1α | Component of heterochromatin | Organismal (HGPS, WS) | Decrease | Fibroblasts, MSCs | Immunostaining, Western blot | H. sapiens |
| Organismal | Decrease | MSCs | Western blot | H. sapiens | ||
| HP1β | Component of heterochromatin | Cellular (senescence) | Increase | Fibroblasts | Immunostaining, Western blot | H. sapiens |
| HP1γ | Component of heterochromatin | Organismal (HGPS) | Decrease | Fibroblasts | Immunostaining | H. sapiens |
| Organismal | Decrease | Fibroblasts | Immunostaining | H. sapiens | ||
| H3K9me1 | Enriched in euchromatin along gene bodies, transcriptional repression | Cellular (senescence) | Increase | Fibroblasts | Western blot, SILAC-MS | H. sapiens |
| H3K9me2 | Enriched in euchromatin along gene bodies, transcriptional repression | Cellular (senescence) | Decrease | Fibroblasts | Western blot, SILAC-MS | H. sapiens |
| Organismal | Decrease | Whole male flies | Western blot | D. melanogaster | ||
| H3K9me3 | Enriched in heterochromatin regions, transcriptional silencing | Organismal (HGPS, WS) | Decrease | Fibroblasts, MSCs | Immunostaining, Western blot, ChIP-seq | H. sapiens |
| Cellular (senescence) | Decrease | Fibroblasts | SILAC-MS, Western blot | H. sapiens | ||
| Organismal | Increase, remodeling | Head | Western blot, ChIP-chip | D. melanogaster | ||
| Organismal | Decrease | Fibroblasts, Soma | Immunostaining, Western blot | H. sapiens, C. elegans | ||
| H3K27me3 | Enriched in euchromatin along gene bodies, transcriptional repression | Organismal (HGPS, WS) | Decrease, remodeling | Fibroblasts, MSCs | Immunostaining, ChIP-Seq | H. sapiens |
| Cellular (senescence) | Remodeling | Fibroblasts | ChIP-Seq | H. sapiens | ||
| Organismal | Decrease | Soma | Western blot | C. elegans | ||
| Organismal | Increase, remodeling | Brain, Muscle stem cells, HSCs | Immunostaining, ChIP-Seq | N. furzeri, M. musculus | ||
| H4K20me2 | DNA repair and genomic stability | Cellular (senescence) | Increase | Fibroblasts | Western blot, SILAC-MS | H. sapiens |
| H4K20me3 | Enriched in pericentric heterochromatin | Organismal (HGPS) | Increase | Fibroblasts | Western blot, Immunostaining | H. sapiens |
| Cellular (senescence) | Decrease | Fibroblasts | Western blot, SILAC-MS | H. sapiens | ||
| Organismal | Increase | Liver, Kidney | Liquid chromatography | R. norvegicus | ||
| H3K4me2 | Enriched in euchromatin along gene body, transcriptional activation | Organismal | Global increase, remodeling | Cortex | ChIP-Seq | M. mulatta |
| H3K4me3 | Enriched in euchromatin at promoters, transcriptional activation | Organismal (WS) | No global change | MSCs | ChIP-Seq | H. sapiens |
| Cellular (senescence) | Remodeling | Fibroblasts | ChIP-Seq | H. sapiens | ||
| Organismal | No change | Soma | Western blot | C. elegans | ||
| Organismal | Decrease, remodeling | Head | ChIP-chip | D. melanogaster | ||
| Organismal | Minor global increase, remodeling | Neurons, HSCs, Muscle stem cells | ChIP-Seq | H. sapiens, M. musculus | ||
| H3K36me3 | Enriched in euchromatin along gene body, transcriptional elongation | Organismal (replicative lifespan) | No global change, remodeling | Yeast cells | ChIP-Seq | S. cerevisiae |
| Organismal | Minor global decrease, remodeling | Soma, Head | Western blot, ChIP-chip, ChIP-Seq | C. elegans, D. melanogaster | ||
| H3K56ac | DNA replication, DNA damage response, nucleosome assembly | Cellular (senescence) | Decrease | Fibroblasts | Immunostaining, Western blot | H. sapiens |
| Organismal (replicative lifespan) | Decrease | Yeast cells | Western blot | S. cerevisiae, | ||
| H4K16ac | Regulation of telomere silencing, regulation of chromatin compaction (?) | Organismal (HGPS) | Decrease | Fibroblasts, Liver | Immunostaining, Western blot | M. musculus |
| Cellular (senescence) | Decrease | Fibroblasts | Western blot | H. sapiens | ||
| Organismal (replicative lifespan) | Increase | Yeast cells | Western blot | S. cerevisiae | ||
| Organismal | Decrease | Liver, Kidney | Western blot | H. sapiens, M. musculus | ||
| H4K12ac | Enriched in euchromatin along gene body, transcriptional elongation | Organismal | Decrease upon contextual fear conditioning | Hippocampus | Western blot | M. musculus |
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see supplementary information S2 (table) for a fully referenced version of this table.
Note that the changes in chromatin reported for WS come from mesenchymal cells derived from an ESC model of WS. Chromatin changes reported for HGPS come from patient-derived cells or a genetic mouse model of the disease.
*
Reported studies of core histone changes correspond to all variants of a particular histone family (not assessed separately).
(?) Functional role of epigenetic mark unclear
§
see supplementary information S1 (box) to read more about targeted and global methods of epigenome mapping
Abbreviations: HGPS: Hutchinson-Gilford Progeria Syndrome; WS: Werner Syndrome; Soma: all body tissues except the germline cells; HSCs: hematopoietic stem cells; MSCs: mesenchymal stem cells; HPLC-MS: high performance liquid chromatography-mass spectrometry; RRBS: reduced representation bisulfite sequencing; WGBS: whole genome bisulfite sequencing; SILAC-MS: Stable isotope labeling by amino acids in cell culture- mass spectrometry; MCAM: methylated CpG island amplification microarrays; ChIP-Seq: Chromatin Immunoprecipitation followed by sequencing; ChIP-chip: Chromatin Immunoprecipitation followed by microarray hybridization; LINE: long interspersed nuclear element; SINE: short interspersed nuclear element; LTR: long tandem repeat.