The key to younger looking skin isn’t in expensive nip/tuck work or clay masks, but as a recent Nature paper shows, it’s actually DNMT1 that plays a major role. Thanks to DNMT1, whenever you shed dry skin, it is continually replaced with a new layer. That’s right—the same DNA methyltransferase that plays a role in hematopoietic and cancer stem cell fate also keeps epithelial progenitor cells chugging along.
Researchers at Stanford and the VA Palo Alto Healthcare System ran DNMT1 through almost every test imaginable. They show that the DNA methyltransferase and the balance of DNA methylation are important for epithelial progenitor-cell self-renewal. That is, DNA methylation (DNMT1 expression) represses differentiation, whereas demethlyation (inhibition or reduction of DNMT1 expression) causes the cells to differentiate and stop being progenitor cells altogether.
Here are a few of the key observations:
- The researchers induced skin cells to differentiate in culture and saw reduced DNMT1 transcript and protein levels. When they looked for DNMT1 protein, they saw it in the basal layer of the epidermis, right where progenitor cells are expected to be.
- In two in vivo tests, human skin with short hairpin RNA constructs targeted to DNMT1 (DNMT1i) didn’t grow well, but control skin grew and could replenish itself.
- Global gene-expression profiles of DNMT1-deficient cells looked a lot like profiles from differentiated cells.
- DNMT1i expression increased Cdk inhibitor levels; these proteins also inhibit stem cell self-renewal.
- MeDIP experiments showed that methylated DNA was enriched in undifferentiated skin cells and occurred in CpG islands and shores.
- Just like DNMT1, UHRF1 (which recruits DNMT1 to hemimethylated DNA) also was in the basal layer of the epidermis and was down-regulated during differentiation. However, Gadd45A and B (which demethylate DNA) were required for differentiation.
Learn all about how to maintain that youthful glow in the full article at Nature, January 2010.