Comparative chromatin accessibility upon BDNF-induced neuronal activity delineates neuronal regulatory elements
Ibarra, I. L.; Ratnu, V. S.; Gordillo, L.; Hwang, I.-Y.; Mariani, L.; Weinand, K.; Hammaren, H. M.; Bulyk, M. L.; Savitski, M. M.; Zaugg, J. B.; Noh, K.-M.
Show abstract
Neuronal activity induced by brain-derived neurotrophic factor (BDNF) triggers gene expression, which is crucial for neuronal survival, differentiation, synaptic plasticity, memory formation, and neurocognitive health. However, its role in chromatin regulation is unclear. Here, using temporal profiling of chromatin accessibility and transcription in mouse primary cortical neurons upon either BDNF stimulation or depolarization (KCl), we identify features that define BDNF-specific chromatin-to-gene expression programs. Enhancer activation is an early event in the regulatory control of BDNF-treated neurons, where the bZIP motif-binding Fos protein pioneered chromatin opening and cooperated with co-regulatory transcription factors (Homeobox, EGRs, and CTCF) to induce transcription. Deleting cis-regulatory sequences decreased BDNF-mediated Arc expression, a regulator of synaptic plasticity. BDNF-induced accessible regions are linked to preferential exon usage by neurodevelopmental disorder-related genes and heritability of neuronal complex traits, which were validated in human iPSC-derived neurons. Thus, we provide a comprehensive view of BDNF-mediated genome regulatory features using comparative genomic approaches to dissect mammalian neuronal activity.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Histone variant H2BE controls activity-dependent gene expression and homeostatic scaling 95%
- MeCP2 Represses the Activity of Topoisomerase IIβ in Long Neuronal Genes 94%
- Integrative transcriptomics reveals sexually dimorphic microRNA control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder 94%
Similar papers in this journal
- A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation 94%
- Mapping chromatin accessibility and active regulatory elements reveals new pathological mechanisms in human gliomas 94%
- DLG2 knockout reveals neurogenic transcriptional programs underlying neuropsychiatric disorders and cognition 94%
Similar papers in this journal
- Transposable elements and their KZFP controllers are drivers of transcriptional innovation in the developing human brain 94%
- Leveraging mouse chromatin data for heritabilityenrichment informs common disease architecture andreveals cortical layer contributions to schizophrenia 94%
- Single cell discovery of m6A RNA modifications in the hippocampus 93%
Similar papers in this journal
- Reliance of neuronal gene expression on cohesin scales with chromatin loop length 94%
- Artificially inserted G-quadruplex DNA secondary structures induce long-distance chromatin activation 93%
- 5-hydroxymethylcytosine mediated active demethylation is required for neuronal differentiation and function 93%
Similar papers in this journal
- Systematic investigation of allelic regulatory activity of schizophrenia-associated common variants 94%
- Cis-regulatory control of transcriptional timing and noise in response to estrogen 93%
- Single nucleus multi-omics links human cortical cell regulatory genome diversity to disease risk variants 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.