Advances in the maintenance mechanism of DNA methylation gene silencing.

On April 10, the Journal of the National Academy of Sciences (PNAS) published an online study paper by the Zhu Bing Group of the Institute of Biophysics of the Chinese Academy of Sciences, roles of the CSE1L-mediated nuclear import in the pathway epigenetic silencing.
the study found that CSE1L, as an important protein in the classical nucleogene transfer pathway in cells, is necessary to maintain the silence of some methylation genes, and further reveals the biological mechanism by which the cell enters the nucleus by selectively transporting specific target proteins into the nucleus to maintain the silencing of specific genes. Gene silencing mediated by
DNA methylation is an important way to regulate gene expression of eukaryotic cells, and plays an important role in regulating the specific expression of gene time and space in organisms and maintaining the stability of transposing elements and other DNA repeat sequences in the genome.
Therefore, it is of great significance to explore and understand the mechanism of the occurrence and maintenance of THE silencing of DNA methylation-mediated genes. the mechanisms of the occurrence and maintenance of the silencing of
DNA methylation mediated genes include DNA methylation inhibition of dna binding DNA, histone deacetylation mediated by methylation CpG binding proteins, sequence-specific inhibitors, histone H3 9th lysine methylation modification, and other proteins that can lead to chromatin tightness.
in order to explore the maintenance mechanism of DNA methylation gene silencing, Zhu Bing's team established a reporting cell line containing EGFP silenced by DNA methylation, discovered a series of proteins that play an important role in maintaining DNA methylation gene silencing through high-throughput screening of genome-wide RNA, and conducted in-depth research on one of its proteins, CSE1L.
CSE1L is one of the important proteins in the cell's classical nuclear transport route, which is responsible for the nuclear transport of the input protein family importin alpha.
knocking down or turning off the expression of CSE1L can activate the reported gene that is silenced by DNA methylation, but does not directly alter the level of methylation of the reported gene and the whole genome.
transcription group analysis found that some endogenous genes that are silenced by DNA methylation are also selectively activated, and that these genes are mainly enriched by genes that rely on the hetone of the protegeide-deacetylase pathway. further studies
found that the nuclei of histone salateacese HDAC1, HDAC2, and HDAC8 were selectively inhibited when CSE1L expression was switched off.
this study enriches the understanding of the mechanism of gene silencing mechanism.
researcher Zhu Bing and associate researcher Zhang Zhuqiang are the communication authors of the thesis, and Dong Qiang, a doctoral student of Zhu Bing's research group, is the first author of the thesis.
Wang Hailin of the Center for Ecological Environment Research of the Chinese Academy of Sciences and Lei Xiaoguang of Peking University participated in the study.
the research was supported by projects from the National Natural Science Foundation of China, the Ministry of Science and Technology and the Chinese Academy of Sciences.
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