Table 1.
Differences in DNA methylation and histone modification levels between young and aged HSCs
| Alterations with age | Functions | Author and year | |
|---|---|---|---|
| DNA methylation | |||
| DNMT1 | Downregulated | Myeloid skewing and self-renewal defects |
Beerman et al. 2013 [10] Sun et al. 2014 [58] Trowbridge et al. 2009 [76] Broske et al. 2009 [75] |
| DNMT3A | Downregulated | Lead to an increase in self-renewal with age at the expense of differentiation |
Beerman et al. 2013 [10] Sun et al. 2014 [58] Challen et al. 2014 [77] |
| DNMT3B | Downregulated | Lead to an even more severe arrest of HSC differentiation |
Sun et al. 2014 [58] Challen et al. 2014 [77] |
| TET1 | Downregulated | Enhance HSC self-renewal; increase B cell production; develop B cell malignancies |
Sun et al. 2014 [58] Cimmino et al. 2015 [73] |
| TET2 | Downregulated | Attenuate differentiation and lead to myeloid transformation and myeloid malignancies |
Busque et al. 2012 [82] Ko et al. 2011 [78] |
| 5-mC | Not studied | Hypermethylation at promoters associated with lineage potential |
Beerman et al. 2013 [10] Oshima et al. 2014 [80] |
| Not studied | Hypermethylation selectively targeting PRC2 and PU.1-binding sites |
Beerman et al. 2013 [10] Sun et al. 2014 [58] Oshima et al. 2014 [80] |
|
| Not studied | Hypomethylation at the HSC fingerprint genes and rRNA genes |
Busque et al. 2012 [82] Oshima et al. 2014 [80] |
|
| 5-hmC | Downregulated | Not studied | Sun et al. 2014 [58] |
| Histone modification | |||
| H3K4me3 | Upregulated | Alter promoter usage and upregulate some genes (Selp, Nupr1, and Sdpr) | Sun et al. 2014 [58] |
| H3K27me3 | Upregulated | Alter promoter usage and downregulate Flt3 expression with age | Sun et al. 2014 [58] |
| H4K16ac | Downregulated | Downregulate nuclear polarity with age |
Florian et al. 2012 [59] Grigoryan et al. 2018 [83] |
| H3K27ac | Downregulated | Link to leukocyte activation and apoptotic signaling |
Grigoryan et al. 2018 [83] Adelman et al. 2019 [15] |
| H3K9me2 | Downregulated | Anchor lamina-associated domains to nuclear lamin A/C |
Grigoryan et al. 2018 [83] Towbin et al. 2012 [84] |
| H3K4me1 | Downregulated | Link to myeloid and erythroid differentiation and functions | Adelman et al. 2019 [15] |
| H3K23ac | Upregulated | Not studied | Cheung et al. 2018 [85] |
| H2BS14ph | Upregulated | Not studied | Cheung et al. 2018 [85] |
| H3K9me2 | Upregulated | Not studied | Cheung et al. 2018 [85] |