0000000000625366
AUTHOR
Magdalena Westphal
Drug-induced chromatin accessibility changes associate with sensitivity to liver tumor promotion
This work explores quantitative chromatin accessibility, transcriptional and cis-acting gene regulatory variations underlying mouse strain–specific differences in drug-induced liver tumor promotion sensitivity.
Loss of the Ca2+/calmodulin-dependent protein kinase type IV in dopaminoceptive neurons enhances behavioral effects of cocaine.
The persistent nature of addiction has been associated with activity-induced plasticity of neurons within the striatum and nucleus accumbens (NAc). To identify the molecular processes leading to these adaptations, we performed Cre/loxP-mediated genetic ablations of two key regulators of gene expression in response to activity, the Ca 2+ /calmodulin-dependent protein kinase IV (CaMKIV) and its postulated main target, the cAMP-responsive element binding protein (CREB). We found that acute cocaine-induced gene expression in the striatum was largely unaffected by the loss of CaMKIV. On the behavioral level, mice lacking CaMKIV in dopaminoceptive neurons displayed increased sensitivity to cocai…