| First Author | Lorsch ZS | Year | 2019 |
| Journal | Nat Neurosci | Volume | 22 |
| Issue | 9 | Pages | 1413-1423 |
| PubMed ID | 31427770 | Mgi Jnum | J:281648 |
| Mgi Id | MGI:6378411 | Doi | 10.1038/s41593-019-0462-8 |
| Citation | Lorsch ZS, et al. (2019) Stress resilience is promoted by a Zfp189-driven transcriptional network in prefrontal cortex. Nat Neurosci 22(9):1413-1423 |
| abstractText | Understanding the transcriptional changes that are engaged in stress resilience may reveal novel antidepressant targets. Here we use gene co-expression analysis of RNA-sequencing data from brains of resilient mice to identify a gene network that is unique to resilience. Zfp189, which encodes a previously unstudied zinc finger protein, is the highest-ranked key driver gene in the network, and overexpression of Zfp189 in prefrontal cortical neurons preferentially activates this network and promotes behavioral resilience. The transcription factor CREB is a predicted upstream regulator of this network and binds to the Zfp189 promoter. To probe CREB-Zfp189 interactions, we employ CRISPR-mediated locus-specific transcriptional reprogramming to direct CREB or G9a (a repressive histone methyltransferase) to the Zfp189 promoter in prefrontal cortex neurons. Induction of Zfp189 with site-specific CREB is pro-resilient, whereas suppressing Zfp189 expression with G9a increases susceptibility. These findings reveal an essential role for Zfp189 and CREB-Zfp189 interactions in mediating a central transcriptional network of resilience. |
