Kamal Nahas in The Scientist:
Transcription factors that tune the expression of multiple genes could be key players in regulating behavior, but scientists need to scout for them. Peter Hamilton, a neuroscientist at Virginia Commonwealth University, has contributed to this search for years, especially in the context of social behavior studies. In 2019, he and his colleagues identified a transcription factor (TF) that correlated with stress resilience in rodents.1 In a recent study, Hamilton and his team discovered that the same TF orchestrates social behaviors in mice and unexpectedly links the brain and immune system.2 Their findings, reported in Translational Psychiatry, shed light on the genetics underpinning social conduct in mammals, laying the groundwork to identify genes contributing to mental illness.
The neural regulator that Hamilton identified in his original study belongs to the largest TF family in mammals, called the Krüppel-associated box (KRAB) zinc finger proteins (ZFP).3 Its members directly regulate genes and repress transposable elements—DNA sequences that regulate other genes.4,5 In the new study, Hamilton and his team explored how the TF in question, ZFP189, affects stress in mice by creating a synthetic version with flipped functionality; they swapped out its repressive domain for an activator one to disrupt its inhibitory effects on transposable elements.
More here.