Project description:Activity-regulated genes (ARGs) are important for neuronal functions like long-term memory and are well-characterized in mammals but poorly studied in other model organisms like Drosophila. Here we stimulated fly neurons with different paradigms and identified ARGs using high-throughput sequencing from brains as well as from sorted neurons: they included a narrow set of circadian neurons as well as dopaminergic neurons. Surprisingly, many ARGs are specific to the stimulation paradigm and very specific to neuron type. In addition and unlike mammalian immediate early genes (IEGs), fly ARGs do not have short gene lengths and are less enriched for transcription factor function. Chromatin assays using ATAC-sequencing show that the transcription start sites (TSS) of ARGs do not change with neural firing but are already accessible prior to stimulation. Lastly based on binding site enrichment in ARGs, we identified transcription factor mediators of firing and created neuronal activity reporters.
Project description:We identified ARGs in a genome-wide manner, in fly brains as well as in sorted neurons; they included dopaminergic neurons (DA) and a subset of circadian-related neurons (PDF+ neurons).
Project description:We identified ARGs in a genome-wide manner, in fly brains as well as in sorted neurons; they included dopaminergic neurons (DA) and a subset of circadian-related neurons (PDF+ neurons).
Project description:We identified ARGs in a genome-wide manner, in fly brains as well as in sorted neurons; they included dopaminergic neurons (DA) and a subset of circadian-related neurons (PDF+ neurons).
Project description:We identified ARGs in a genome-wide manner, in fly brains as well as in sorted neurons; they included dopaminergic neurons (DA) and a subset of circadian-related neurons (PDF+ neurons).
Project description:We identified ARGs in a genome-wide manner, in fly brains as well as in sorted neurons; they included dopaminergic neurons (DA) and a subset of circadian-related neurons (PDF+ neurons).
Project description:Experience-dependent gene transcription is required for nervous system development and function. However, the DNA regulatory elements that control this program of gene expression are not well defined. Here we characterize the enhancers that function across the genome to mediate activity-dependent transcription in mouse cortical neurons. We find that the subset of enhancers enriched for monomethylation of histone H3 Lys4 (H3K4me1) and binding of the transcriptional coactivator CREBBP (also called CBP) that shows increased acetylation of histone H3 Lys27 (H3K27ac) after membrane depolarization of cortical neurons functions to regulate activity-dependent transcription. A subset of these enhancers appears to require binding of FOS, which was previously thought to bind primarily to promoters. These findings suggest that FOS functions at enhancers to control activity-dependent gene programs that are critical for nervous system function and provide a resource of functional cis-regulatory elements that may give insight into the genetic variants that contribute to brain development and disease.