The 844th MIB Seminar
(Joint Usage/Research Center for the Multi-stratified Host Defense System)
Title
A long non-coding enhancerRNA forms Triple-strand genome structure, R-loops, to shape emotional experience-induced behavioral adaptation
Speaker
Makoto Taniguchi (Ph.D.)
Assistant Professor
Department of Neuroscience, Medical University of South Carolina
Date
May. 28 (Tue), 2024
16：00〜17：00
Venue
Seminar Room, Main Building 1F, Medical Institute of Bioregulation, Hospital Campus
No.30 on the map.
Abstract
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. We discovered that a conserved, long non-coding enhancer RNA (lnc-eRNA) transcribed from an activity-sensitive enhancer produces RNA:DNA hybrid R-loop structures that support 3D chromatin-looping of the enhancer and proximal promoter and stimulus-induced, rapid Npas4 gene induction. We also show that this Npas4 lnc-eRNA is required for the development of behavioral adaptations produced by chronic psychosocial stress or cocaine exposure, revealing a critical role for this new genomic regulatory mechanism in the transmission of emotional experiences, such as stress or drug use, to adaptive behavioral responses.
References
- Chao Y.S. et al.
Innate cocaine-seeking vulnerability arising from loss of serotonin-mediated aversive effects of cocaine in rats. Cell Report 42(5):112404, 2023. - Hughes B.W. et al.
NPAS4 in the medial prefrontal cortex mediates chronic social defeat stress-induced anhedonia-like behavior and reductions in excitatory synapses. Elife 12:e75631, 2023. - Taniguchi M. et al.
HDAC5 and Its Target Gene, Npas4, Function in the Nucleus Accumbens to Regulate Cocaine-Conditioned Behaviors. Neuron 96:130-144, 2017. - Smith L.N. et al.
Fragile X mental retardation protein regulates synaptic and behavioral plasticity to repeated cocaine administration. Neuron 82:645-658, 2014.
Contact
Institute for Advanced Study / Medical Institute of Bioregulation
Tetsuya Takano
TEL: 092 (642) 4201