Druggable Transcriptional Networks in the Human Neurogenic Epigenome.

Druggable Transcriptional Networks in the Human Neurogenic Epigenome. Pharmacol Rev. 2019 Oct;71(4):520-538 Authors: Higgins GA, Williams AM, Ade AS, Alam HB, Athey BD Abstract Chromosome conformation capture methods have revealed the dynamics of genome architecture which is spatially organized into topologically associated domains, with gene regulation mediated by enhancer-promoter pairs in chromatin space. New evidence shows that endogenous hormones and several xenobiotics act within circumscribed topological domains of the spatial genome, impacting subsets of the chromatin contacts of enhancer-gene promoter pairs in cis and trans Results from the National Institutes of Health-funded PsychENCODE project and the study of chromatin remodeling complexes have converged to provide a clearer understanding of the organization of the neurogenic epigenome in humans. Neuropsychiatric diseases, including schizophrenia, bipolar spectrum disorder, autism spectrum disorder, attention deficit hyperactivity disorder, and other neuropsychiatric disorders are significantly associated with mutations in neurogenic transcriptional networks. In this review, we have reanalyzed the results from publications of the PsychENCODE Consortium using pharmacoinformatics network analysis to better understand druggable targets that control neurogenic transcriptional networks. We found that valproic acid and other psychotropic drugs directly alter these networks, in...
Source: Pharmacological Reviews - Category: Drugs & Pharmacology Authors: Tags: Pharmacol Rev Source Type: research