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| 2023-09-07 14:09:10 | onclick： | Scientists Reveal Genetic Effects of Prohistone on Cell Differentiation Destiny |
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There are about 200 cell types in the body, all developed from the same fertilized egg, with almost exactly the same genomic information, but with very different morphologies and functions.Recent studies have found that epigenomic maps are crucial for determining cell identity.But one major question remains: how do cell division species, the epigenomic information, pass on and sustain cell fate?
On September 4th, the team of Gan Haiyun, Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, found that the symmetrical distribution and inheritance of prohistones with epigenomic information ensured differentiation and early mouse embryo development.
"This genetic regulation study is not just about stabilizing established cell states," Pablo Navarro, a professor at Sidai University in Paris, said in a feature review with Nature Genetics.Instead, it strongly promotes the dynamic changes needed for development.”
Revealing the Symmetrical Distribution Mechanism of Parent Histone
The basic structural unit of chromatin is nucleosome, which consists of octamer proteins formed by four histones (H2A, H2B, H3, H4) and DNA strands wound around them.Modification of histone tail structure (such as methylation and acetylation) is an important part of epigenome, which can influence gene expression by regulating chromatin structure.
During individual development, cells undergo several divisions, and for each division, DNA and histones need to be multiplied.Semi-retention replication of DNA can maintain genomic consistency between parent and child generations, but little is known about how histones are transferred between parent and child generations.
Previously, Gan and his collaborators have revealed the molecular mechanisms of parental histone distribution during DNA replication.That is, the parent histones are transferred to the leading chain by Pole3 and Pole4 and to the lagging chain by the Mcm2-Ctcf4-Pola1 axis, which ensure the symmetrical distribution of histone modification on sister chromatids.However, the biological significance of this distribution in regulating epigenetic state and distribution process remains to be clarified.
In this study, Gan Haiyun's team obtained mouse embryonic stem cells that lacked MCM2 histone binding function through point mutation (Mcm2-2A:Y81A/Y90A).It was found that the distribution of prohistoproteins in MCM2 mutant cells was out of balance, and the distribution of histone modification throughout the genome was abnormal.Mcm2-2A homozygous mouse embryo development defect early, embryo death.
This indicates that the symmetrical distribution and inheritance of prohistone are important for embryonic stem cell differentiation and early mouse embryo development.
Histone Genetics Affects Cell Differentiation Destiny
Further studies have shown that histone genetic imbalance can lead to increased epigenomic disturbance and genetic heterogeneity.Abnormalities in the epigenome can lead to abnormalities in cell transcriptional groups, especially genes associated with development, which in turn leads to abnormalities in differentiation and development.
After histone transmission, the development of the fertilized eggs in mice became problematic at a very early stage and stagnated at the blastocyst stage.Gan Yunhai, the paper's correspondent, explains.
In addition, the study found that abnormal distribution of histone variants (H3.3) involved in histone modification (H3K27me3) model also influences the inheritance of histone modification landscape and changes the fate of cell differentiation.
Professor Zhang Zhiguo of Columbia University said: "This study is the first in mammals to demonstrate that symmetrical transmission of histone modifications on DNA strands during DNA replication is one of the fundamental characteristics of differentiation.”
Li Guohong, a researcher at Wuhan University's School of Life Sciences and Institute of Biophysics, Chinese Academy of Sciences, commented: "This work is cleverly designed to demonstrate the importance of parental histones carrying a lot of epigenetic information.
It is reported that the discovery has important scientific significance and potential contribution to understanding the distribution and inheritance of epigenetic information in cell division.
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