Manipulating histone H3.3 may erase cell "memory"

Taking out a mature cell and removing its identity, so that it can become any kind of cell-nuclear reorganization, has broad prospects in repairing damaged tissue and replacing bone marrow after chemotherapy. The 2012 Nobel Prize winner in medicine Dr. John Gordon's latest paper published in the journal Epigenetics and Chromatin Research shows that the histone H3.3 stored by the Hira protein restores the nuclear pluripotency Development has become a critical step for many cell types.

All individual cells have the same DNA (deoxyribonucleic acid). As the organism matures, these cells can be recombined into different types such as heart, lung, and brain. To achieve this goal, different genes are more or less permanently shut down in each cell lineage. As the embryo grows, after a certain amount of differentiation, cells that go down a certain path will no longer become other things. For example, heart cells cannot be transformed into lung tissue, and muscle cells cannot form bones.

One method of recombinant DNA is to transfer the nucleus of a mature cell to an unfertilized egg. The proteins and other factors in the egg will cause the DNA to turn on certain genes while turning off other genes until it resembles the DNA of a multipotent cell. However, it seems not easy to completely erase the "memory" of the cells in this way.

One of the mechanisms regulating gene activity is chromatin, especially histones. DNA is entangled in histones, and changes in the way it entangles will change the genes available to the cell. In order to understand the working principle of nuclear reorganization, the research team led by Dr. Gordon transplanted the nucleus of mice into frog oocytes, and added fluorescently labeled histones through microinjection to observe histones in cells and nucleus Where to gather inside.

Using a real-time microscope, the research team clearly observed that from the 10th hour, H3.3 histones (participating in gene activation) expressed in oocytes began to be incorporated into the transplanted nuclei. When the researchers looked at the details of the Oct4 gene (which is involved in the formation of cell pluripotency), they found that H3.3 histones were also incorporated into Oct4, and at the same time the gene began to transcribe. The team also found that Hira histones (which require H3.3 to enter chromatin in concert) also require nuclear reorganization.

Genetic experts point out that manipulating the path of H3.3 may provide a new method for completely erasing the "memory" of cells and producing a truly pluripotent cell. Studies have shown that chromatin is the key to preventing artificially induced recombination commonly used in the clinic.

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