Chinese Scientists Demonstrated the Mechanism of How Heterochromatin Relaxer Gadd45a Opens Up Mirna During Pluripotency Acquirement

On October 12, Xingguo Liu’s laboratory at the Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences published an article online entitled “Gadd45a opens up the promoters regions of miR-295 facilitating pluripotency induction” in Nature publisher journal Cell Death and Disease. Scientists discovered that heterochromatin relaxer Gadd45a relaxes the promoter regions of miR-295 and increases the expression of miR-295 during reprogramming, showing a novel concise targeting of Gadd45a in noncoding RNA in cell-fate determination.

MicroRNAs (miRNAs) are endogenous short noncoding RNAs that regulate gene expression and control many physiological processes including development, homeostasis and metabolism. Recent studies have revealed that miRNAs play critical roles in pluripotency maintenance and somatic cell reprogramming. However, the molecular mechanisms controlling miRNAs during somatic cell reprogramming remain obscure.

Previously, Xingguo Liu’s labratory found that Gadd45a could relax the promoter regions of pluripotency genes and promote their expression during reprogramming. In this study, they showed that Gadd45a likewise promotes the expression of miR-295, providing further evidences for the function of Gadd45a in chromatin relaxation. Furthermore, they show that Gadd45a binds the promoter regions of miR-295 and opens the promoter regions of miR-295. Their results demonstrate that Gadd45a regulates the expression of genes and noncoding RNAs by acting on chromatin. It will be interesting to test whether Gadd45a also regulates other noncoding RNAs such as lncRNAs, piwiRNAs.

Gadd45 (growth arrest and DNA-damage-inducible protein 45a) is a potential RNA-binding protein involved in many cellular processes including cell cycle, senescence, tumor progression, DNA repair and active DNA demethylation. The expression of Gadd45a has been detected in many mammalian cells, and the rapid induction of Gadd45a upon environmental stress and drug therapies has been observed in every cell type tested to date, which is a protective mechanism against DNA damage. miR-290 cluster is highly expressed in mESCs and participate in the self-renew of pluripotent stem cells and embryonic development by controlling cell cycles and pluripotent genes expression. Their findings suggest Gadd45a may cooperates with the miR-290 cluster to regulate embryonic development, stress reaction and many other physiological processes.