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Um, D.

Publications and source records attributed to Um, D..

2 recordsLinked to original sources

Npas4-mediated dopaminergic regulation of fear memory states

Amygdala circuitry encodes associations between conditioned stimuli and aversive unconditioned stimuli, and also controls fear expression (Pape and Pare, 2010). However, whether and how irrelevant information for unpaired conditioned stimuli (CS-) is discretely processed, and how it was influenced by stress remain unknown. CS- memory is retrievable immediately after fear conditioning, but then becomes silent after memory consolidation in mice. Synaptic pathway from the lateral to the anterior basal amygdala gates the expression of CS- memory, depending upon Npas4-mediated Drd4 synthesis. The upregulation of Npas4-Drd4 axis, which is precluded by corticosterone, shifts functional states of neural engrams for CS- memory toward silent states and limits its retrievability. In here, we demonstrate the cellular and molecular mechanisms regulating the functional states of neural engrams, which can be switched or maintained, supporting discriminative memory.

neuroscience↗

Enhancer RNAs stimulate Pol II pause release by harnessing multivalent interactions to NELF

Enhancer RNAs (eRNAs) are long non-coding RNAs that originate from enhancers. Although eRNA transcription is a canonical feature of activated enhancers, the molecular features required for eRNA function and the mechanism of how eRNAs impinge on target gene transcription have not been established. Thus, using eRNA-dependent RNA polymerase II (Pol II) pause release as a model, we examined the requirement of sequence, structure and length of eRNAs for their ability to stimulate Pol II pause release by detaching NELF from paused Pol II. We found eRNA not to exert their function through common structural or sequence motifs. Instead, efficient NELF release requires a single eRNA molecule that must contain unpaired guanosines to make multiple, allosteric contacts with several NELF subunits. By revealing the molecular determinants for eRNA function, our study mechanistically links eRNAs to Pol II pause release and provides new insight into the regulation of metazoan transcription.

biochemistry↗