Title : Mechanism of C/EBP? core transcriptional regulatory loop driven by super-enhancer to promote dedifferentiation of schwann cells
Abstract:
The effect of nerve regeneration after peripheral nerve injury is closely related to the functional state of Schwann cells (SCs), especially related to interactions between enhancers and transcription factors. Our current study found that mRNA expression of C/EBPβ in the early stage of sciatic nerve injury in SD rats was significantly up-regulated, which promoted the dedifferentiation of SCs. H3k27ac-ChIP showed there is a super-enhancer (SE) region near C/EBPβ. After inhibiting Brd4, which is the core element of SE, the upward trend of C/EBPβexpression was significantly inhibited. Motif prediction found that C/EBPβ could form a core transcriptional regulatory circuit (CRC). Therefore, we speculate that the CRC loop in SCs formed by C/EBPβthrough SE plays a synergistic role in promoting nerve regeneration. This study intends to up-/down-regulate C/EBPβ through in vivo and in vitro experiments, to understand the expression of C/EBPβon the dedifferentiation of SCs and the repair process after peripheral nerve injury, and to examine biological effects of CRC in SCs. If this hypothesis is confirmed, it will not only provide a new insight for understanding nerve regeneration, but also provide a scientific basis for how to treat peripheral nerve injury more effectively, so as to better find molecular therapeutic targets.
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.
