Blood profiling in 120 donors showed that age-related changes in DNA methylation and chromatin accessibility usually do not coincide
Blood profiling in 120 donors showed that age-related changes in DNA methylation and chromatin accessibility usually do not coincide
In a preprint posted on July 27, Mara Steiger and colleagues studied blood from healthy people aged 19–78 years. They compared DNA methylation with chromatin accessibility and, in smaller subsets, also analyzed the CTCF protein and five histone marks.
Cells from the same person have the same DNA sequence, but different cells read different genes from it. The epigenome regulates this process through methyl groups on DNA, the packaging of DNA with proteins, and marks on the packaging proteins themselves. Chromatin accessibility indicates which regions of DNA can be reached by proteins that activate genes.
Steiger and colleagues examined how often these age-related shifts coincided in blood. In samples from 120 donors, they identified 618 DNA positions where methylation changed with age. In 91 samples, chromatin accessibility changed across 33 724 regions. The same genomic locations contained about 3% of the age-related CpG sites and 10% of the regions showing coordinated changes in methylation.
A CpG site is a position in DNA where a cell can add a methyl group. At most of the identified locations, methylation and chromatin accessibility changed in different regions of the genome. Overlap was uncommon. The examples reported by the authors included regions near ELOVL2, GATA2, FOXP1, and IGFBP7.
The authors also compared CTCF, a protein that helps organize chromosomes, and five histone marks in five young and five older donors. At most age-related CpG sites and regions of accessible chromatin, the CTCF and histone mark signals did not change in parallel. In this blood map, age-related changes across different layers of the epigenome diverged more often than they coincided.
In the same cohort, one algorithm predicted age from methylation with a mean error of 2,56 years. However, this estimate was based only on DNA marks. It did not describe chromatin accessibility, histone marks, or gene activity. Therefore, in rejuvenation experiments, an epigenetic clock estimate cannot replace measurements of other layers in the same tissue. In this study, those layers changed in different regions of the genome.