{"doi":"10.1101/2023.12.20.572697","title":"Egr1 is a sex-specific regulator of neuronal chromatin, synaptic plasticity, and behaviour","abstract":"Sex differences are found in brain structure and function across species, and across brain disorders in humans 1-3 . The major source of brain sex differences is differential secretion of steroid hormones from the gonads across the lifespan 4 . Specifically, ovarian hormones oestrogens and progesterone are known to dynamically change structure and function of the adult female brain, having a major impact on psychiatric risk 5-7 . However, due to limited molecular studies in female rodents 8 , very little is still known about molecular drivers of female-specific brain and behavioural plasticity. Here we show that overexpressing Egr1, a candidate oestrous cycle-dependent transcription factor 9 , induces sex-specific changes in ventral hippocampal neuronal chromatin, gene expression, and synaptic plasticity, along with hippocampus-dependent behaviours. Importantly, Egr1 overexpression mimics the high-oestrogenic phase of the oestrous cycle, and affects behaviours in ovarian hormone-depleted females but not in males. We demonstrate that Egr1 opens neuronal chromatin directly across the sexes, although with limited genomic overlap. Our study not only reveals the first sex-specific chromatin regulator in the brain, but also provides functional evidence that this sex-specific gene regulation drives neuronal gene expression, synaptic plasticity, and anxiety- and depression-related behaviour. Our study exemplifies an innovative sex-based approach to studying neuronal gene regulation 1 in order to understand sex-specific synaptic and behavioural plasticity and inform novel brain disease treatments.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":391597,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1164826,"name":"Eric Purisic","orcid":null,"position":1,"is_corresponding":false},{"id":1164385,"name":"Eduardo F. Gallo","orcid":"0000-0001-9906-1425","position":2,"is_corresponding":false},{"id":275114,"name":"John M. Greally","orcid":"0000-0001-6069-7960","position":3,"is_corresponding":false},{"id":585984,"name":"Masako Suzuki","orcid":"0000-0003-0605-9225","position":4,"is_corresponding":false},{"id":27844,"name":"Marija Kundaković","orcid":"0000-0002-6734-4217","position":5,"is_corresponding":false},{"id":746356,"name":"Devin Rocks","orcid":"0000-0002-3192-0219","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T01:18:47.408273Z","pmid":"38187614","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}