Stress resilience is promoted by a Zfp189-driven transcriptional network in prefrontal cortex.

ABSTRACT: 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 methyltrans

SUBMITTER: Lorsch ZS 

PROVIDER: S-EPMC6713580 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature