Project description:Axon regeneration is a necessary step toward functional recovery after spinal cord injury. The AP-1 transcription factor c-Jun has long been known to play an important role in directing the transcriptional response of Dorsal Root Ganglion (DRG) neurons to peripheral axotomy that results in successful axon regeneration. Here we performed ChIPseq for Jun in mouse DRG neurons after a sciatic nerve crush or sham surgery in order to measure the changes in Jun’s DNA binding in response to peripheral axotomy. We found that the majority of Jun’s injury-responsive changes in DNA binding occur at putative enhancer elements, rather than proximal to transcription start sites. We also used a series of single polypeptide chain tandem transcription factors to test the effects of different Jun-containing dimers on neurite outgrowth in cortical and hippocampal neurons. These experiments demonstrated that dimers composed of Jun and Atf3 promoted neurite outgrowth in rat CNS neurons. Our work provides new insight into the mechanisms underlying Jun’s role in axon regeneration.
Project description:To investigate the role of ATF3 in vascular endothelial cells, gene expression profiling analysis was performed using RNA-seq data from human retinal microvascular endothelial cells (HRMECs) transfected with ATF3 siRNA.
Project description:To examine the effects of phosphorylated JUN-mediated enhancers activation on gene expression, we conducted RNA-seq analysis in JUN wildtype (WT) or JUN inactive mutant (JUN AA) overexpressed MRC5 cells. The expression levels of genes associated with JUN-activated enhancers are significantly upregulated in JUN WT cells rather than in JUN AA cells. To quantify the effects of JUN inactivation on gene expression, we also performed RNA-seq analysis in JNKi-treated induced CAFs (iCAFs). We observed that JNKi significantly reduced expression levels of JUN-activated enhancers-associated genes.