Unlocking the secrets of liver regeneration with epigenetics
New research uncovers a novel mechanism for epigenetic compensation that enhances regeneration of liver cells. This provides new insights into the precise mechanisms behind regenerative patterns of gene expression.
The liver is the only solid organ in mammals with the ability to regenerate. Despite decades of research, the precise mechanisms and gene expression patterns that confer this property are yet to be determined. However, a new study carried out by researchers at New York University (Abu Dhabi, United Arab Emirates) and published in Developmental Cell has discovered a novel mechanism of epigenetic compensation that primes and promotes liver regeneration in mice.
When suppressor genes are removed, epigenetic marks replace them and prevent disturbed gene expression in the cell – this is known as epigenetic compensation. Within the study, researchers removed UHRF1 – a key epigenetic regulator essential for DNA methylation – from mouse livers and found that when parts of the liver had been surgically removed, an enhanced liver regeneration response was detected. This unexpected response came as a result of earlier and more sustained activation of pro-regenerative genes and a decrease in DNA methylation.
Further experiments confirmed that the increase in regenerative ability was also caused by another level of genome protection from the repressive epigenetic mark, H3K27me3. Thus, the redistribution of H3K27me3, removed from its function of repressing regenerative genes, resulted in livers lacking UHFR1 to regenerate faster.
Sadler Edepli (New York University) explained, “When H3K27me3 compensates for the loss of DNA methylation, this results in a favorable epigenetic environment for liver regeneration. It will be exciting to explore whether drugs that can modify the epigenome have the potential to induce epigenetic compensation and increase the liver’s ability to regenerate in cases of liver disease or failure.”
Wang S, Zhang C, Hasson D et al. Epigenetic compensation promotes liver regeneration. Dev. Cell. doi:10.1016/j.devcel.2019.05.034 (2019) (Epub ahed of print);