A long noncoding eRNA forms R-loops to shape emotional experience-induced behavioral adaptation.

Autor: Akiki RM; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.; Medical Scientist Training Program, Medical University of South Carolina, Charleston, SC, USA., Cornbrooks RG; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA., Magami K; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA., Greige A; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.; Medical Scientist Training Program, Medical University of South Carolina, Charleston, SC, USA., Snyder KK; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA., Wood DJ; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.; Medical Scientist Training Program, Medical University of South Carolina, Charleston, SC, USA., Herrington MC; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA., Mace P; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA., Blidy K; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA., Koike N; Department of Physiology and Systems Bioscience, Kyoto Prefectural University of Medicine, Kyoto, Japan., Berto S; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA., Cowan CW; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA., Taniguchi M; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 Dec 13; Vol. 386 (6727), pp. 1282-1289. Date of Electronic Publication: 2024 Dec 12.
DOI: 10.1126/science.adp1562
Abstrakt: Emotional experiences often evoke neural plasticity that supports adaptive changes in behavior, including maladaptive plasticity associated with mood and substance use disorders. These adaptations are supported in part by experience-dependent activation of immediate-early response genes, such as Npas4 (neuronal PAS domain protein 4). Here we show that a conserved long noncoding enhancer RNA (lnc-eRNA), transcribed from an activity-sensitive enhancer, produces DNA:RNA hybrid R-loop structures that support three-dimensional chromatin looping between enhancer and proximal promoter and rapid Npas4 gene induction. Furthermore, in mouse models, Npas4 lnc-eRNA and its R-loop are required for the development of behavioral adaptations produced by chronic psychosocial stress or cocaine exposure, revealing a potential role for this regulatory mechanism in the transmission of emotional experiences.
Databáze: MEDLINE