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. Author manuscript; available in PMC: 2016 Oct 1.
Published in final edited form as: Nat Rev Mol Cell Biol. 2015 Sep 16;16(10):593–610. doi: 10.1038/nrm4048

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
¥

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.