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Table 1 Differences in DNA methylation and histone modification levels between young and aged HSCs

From: Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

 

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]