Title : Pioneer transcription factor Runx2 affecting biological function of schwann cells via self-inducible reconstruction of silencer to remodel chromotin
Abstract:
The repair and regeneration of injured peripheral nerves is a difficult problem in modern medicine. In the current experiment, we found that the expression of Runx2 in Schwann cells (SCs) increased significantly in the early stage of injury after injury, and single-cell sequencing suggested that Runx2 might play an important role in regulating the biological function of SCs. Pioneer transcription factors (pTFs) are a class of master transcription factors that can affect the opening of chromatin, thus affecting gene expression. After overexpression of Runx2 in SCs, Runx2 can independently action without histone modification, and execute positive feedback up-regulating gene expression of itself, and selectively close the functional frame of chromatin. Therefore, we speculate that Runx2 can act as pTFs to reconstruct SS and regulate SCs phenotype. In this study, we intend to regulate the expression of Runx2 in cells in vitro and in vivo to verify the effect of Runx2 on the phenotype; By detecting the histone modification and the binding of transcription factors in Runx2 overexpression SCs, it is verified that Runx2, as a pTFs, can change the chromatin landscape, construct the epigenetic mechanism of silencer to limit interactions of other transcription factors, and finally affect the fate of SCs. If it could be well proved, it would probably lay an important foundation for mechanism study of peripheral nerve repair after injury.
Audience Take Away Notes:
- Epigenetics is the discipline that studies the mechanisms by which genetic information related to traits is preserved and transmitted to offspring through pathways such as DNA methylation and chromatin conformational changes in non DNA sequence changes.
- At present, there is relatively little epigenetic research on peripheral nervous system damage and repair processes, mainly focusing on phenotype research. If this research approach can be promoted, it can better understand the regulatory mechanisms of damage repair and guide the identification of more optimal quality targets to promote nerve regeneration.