Stella, the first guarantee factor for normal established DNA methylation levels in the egg cell genome.

A research paper by The Institute of Biophysics of the Chinese Academy of Sciences, Stella Safeguards the oocyte methylome by the patient ing de novo methylation mediated by DNMT1, was published online November 28 in the journal Nature.
the study found Stella, the first safeguard factor in the normal establishment of DNA methylation levels in the egg cell genome.
Stella protein protects the unique low methylation characteristics of the egg genome, ensuring the correct expression of the mother gene in the early embryo and the normal development of the early embryo.
only a limited number of eggs can be provided in the lifetime of a female mammal.
the dna methylation level sharply in the egg, only about half the DNA methylation level of sperm and most end-of-life differentiated somatic cells.
however, it is not clear how this unique DNA methylation state of the egg is formed, what factors are regulated, and what biological significance it has.
in the team's previous study, the researchers screened a new DNA methylation regulatory gene, Stella, from the cDNA library of mouse egg cells.
expression of Stella in somatic cells creates a complex by the DNA methylation regulatory factor UHRF1, which interferes with the maintenance of DNA methylation modification during the silk yite process.
Because Stella is highly expressed in oocytes, in this effort, the researchers explored Stella's function during the maturation of oocytes and found that Stella prevented UHRF1 from accumulating in the nucleus of the oocyte through an active nuclear transfer process.
Stella knocked out the female mice's oocytes with abnormal accumulation of UHRF1 nuclei, excessive DNA methylation, and doubled the methylation level of the mature egg genome to a level similar to that of sperm DNA methylation.
the low DNA methylation state of the egg genome is different from almost any other cell type, and the study found the first regulatory factor to protect the unique methylation state of the egg.
previous studies have shown that Stella is not necessary for processes such as egg formation, ovulation and fertilization, but eggs from Stella knockout female mice do not develop properly before bed after fertilization, leading to female infertility.
the study found that abnormally high methylation caused by Stella's absence occurred mainly in the silent genomic region, and although abnormal methylation of these gene promoters did not interfere with the egg process, it seriously affected the quality of mature eggs and the activation of the mother genome of the mother-stage embryo after fertilization.
interesting, it is previously known that the loss of almost all OF THE eggs with DNA methylation does not affect the embryo's pre-bed development, so the scientific community has thought that the specific DNA methylation status of the egg is not important.
, the work shows that methylation spectrum specific to the mother genome is critical to development, but is not important in protecting those areas of methylation, but in protecting those non-methylation regions in this unique state of demethylation.
the study reveals the biological significance of the egg's unique genomic low methylation state.
in addition, DNA methylated dNMT1 has long been considered a maintenance methylated enzyme, using only semi-methylated DNA as a substrate in cells.
the study found that abnormal methylation in Stella's missing egg cells was catalyzed by DNMT1, the first conclusive evidence that DNMT1 has the ability to establish DNA methylation from the beginning without relying on the original methylation.
this finding rewrites textbook classification of DNA methylated enzymes.
more important, this finding provides a functional explanation for the high expression of DNMT1 in many types of cells in the body that have exited the cell cycle, such as oocytes and neurons, and provides important implications for the significance of DNMT-responsible DNA methylation in the aging process.
Zhu Bing is the communication author of the paper, Zhu Bing group doctoral student Li Yingfeng, Ph.D. Zhang Zhuqiang and Tongji University Gao Shaorong Group Ph.D. Chen Jiayu are the co-first authors of the thesis.
Gao Shaorong of Tongji University, Wang Hailin Oferin Of the Center for Ecological Environment Research of the Chinese Academy of Sciences, Wang Zhigao Task Force of Southwest Medical Center of the United States, Xu Guoliang Of the Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, Ong Jiemin Of East China Normal University, Fan Guoping Ofucla of the University of California, And Zhang Pumin of Baylor College of Medicine, USA, participated in the cooperative study.
the research was supported by the National Natural Science Foundation of China, the Ministry of Science and Technology, the Chinese Academy of Sciences and the Shanghai Science and Technology Commission.
Source: Institute of Biophysics.