Abstract
SummarySpatiotemporal regulation of gene expression depends on the cooperation of multiple mechanisms, including the functional interaction of promoters with distally located enhancers. Here, we show that, in cortical neurons, a subset of short interspersed nuclear elements (SINEs) located in the proximity of activity-regulated genes bears features of enhancers. Enhancer SINEs (eSINEs) recruit the Pol III cofactor complex TFIIIC in a stimulus-dependent manner and are transcribed by Pol III in response to neuronal depolarization. Characterization of an eSINE located in proximity to the Fos gene (FosRSINE1) indicated that the FosRSINE1-encoded transcript interacts with Pol II at the Fos promoter and mediates Fos relocation to Pol II factories, providing an unprecedented molecular link between Pol III and Pol II transcription. Strikingly, knockdown of the FosRSINE1 transcript induces defects of both cortical radial migration in vivo and activity-dependent dendritogenesis in vitro, demonstrating that FosRSINE1 acts as a strong enhancer of Fos expression in diverse physiological contexts.
Highlights
All organisms respond to environmental conditions by modifying gene expression in a manner that is strictly regulated both temporally and spatially
Genome-wide Occupancy of the Pol III Machinery Identifies Enhancer SINEs (eSINEs) In response to neuronal depolarization, a group of short interspersed nuclear elements (SINEs) located near activity-dependent genes undergoes de novo acetylation at H3K9/K14 (Crepaldi et al, 2013)
Gtf3c1 binding to eSINEs increased in response to stimulation (p < 2.2eÀ16, Mann-Whitney test), whereas it was unchanged for rndSINEs
Summary
All organisms respond to environmental conditions by modifying gene expression in a manner that is strictly regulated both temporally and spatially. This adaptive response is of fundamental importance for any cell type, it is relevant to neurons. Pol III complexes bind preferentially to genomic regions adjacent to Pol II transcriptional start sites (TSSs) (Moqtaderi et al, 2010; Oler et al, 2010), and expressed tRNA genes are predominantly located in the vicinity of active Pol II promoters (Oler et al, 2010). Pol III and Pol II transcription may be functionally linked
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