Cell Death and Disease: Research Reveals Heterochromatin Loose Factor "Unlocking - WeChat" Mode
Release date: 2017-10-20
On October 12, Liu Xingguo, research group of Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, published the research paper on Gadd45a open up the promoters regions of miR-295 facilitating pluripots. It was published online in Cell Death and Disease. The researchers found that during somatic cell reprogramming to induce pluripotent stem cells, the heterochromatin loose factor Gadd45a specifically binds to the miR-295 promoter and opens the promoter region, activating the expression of miR-295, thereby increasing reprogramming efficiency. The study reveals that Gadd45a precisely targets the new pathway of miR-290 cluster to regulate cell fate turnover, and is a new mode in which non-coding RNA is precisely opened at chromatin level.
Short-chain non-coding RNAs (miRNAs) are involved in the regulation of various physiological and pathological processes such as development, metabolism, and cancer. In recent years, studies have reported that miRNAs play an important role in pluripotency maintenance and cell programming and reprogramming. However, the epigenetic mechanism of how miRNAs are regulated in chromatin levels in cell fate regulation remains unclear.
The research team published a paper on EMBO Reports, and screened the heterochromatin loose factor Gadd45a as a new factor to develop a new and more efficient reprogramming method. The team used a transcriptomic system to identify the miRNA targets of Gadd45a and found that Gadd45a specifically activates the expression of miR-290 clusters during somatic cell reprogramming. Further research by the research team found that Gadd45a enhances the reprogramming by binding to the promoter of miR-295 and opening the chromatin of the promoter region, raising the levels of H3K9Ac and H3K27Ac in this region, activating the expression of miR-295. effectiveness. This is like the pluripotency of cells. The miR-295 "miRNA signal" is required, but it is locked by heterochromatin and cannot be emitted. Gadd45a opens the promoter regions. The "WeChat" miR-295 was issued to help cells build pluripotency. This work is a new mode of "opening the promoter regions-miRNA signal" in which non-coding RNA is precisely turned on at the chromosomal level in cell fate regulation.
The discovery of this novel pathway for the precise action of the Gadd45a-miRNA290 cluster in cell fate regulation is of great significance. Gadd45a protein (growth inhibition and DNA damage-inducing protein) is an important stress factor, which is highly expressed in the presence of ultraviolet, hypoxia, high temperature, osmotic pressure, radiation and other environmental and drug stresses; and in development, aging, cancer and other physiology It plays an important role in pathology. The mechanism of action of Gadd45a is mainly involved in the regulation of cell cycle and DNA damage repair. The miR-290 cluster is highly expressed in pluripotent stem cells, and participates in pluripotent stem cell self-renewal and early embryo development by regulating cell cycle and pluripotency gene expression. The newly discovered Gadd45a and miR-290 clusters are precisely applied to the above. A variety of stress, development, and pathological conditions may play an important role.
The research work was supported by the Ministry of Science and Technology, the Chinese Academy of Sciences, the National Natural Science Foundation, Guangdong Province and Guangzhou City.
Source: Guangzhou Biological Institute
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