{"doi":"10.1101/gad.352889.125","title":"MEF2C controls segment-specific gene regulatory networks that direct heart tube morphogenesis","abstract":"The gene regulatory networks (GRNs) that control early heart formation are beginning to be understood, but lineage-specific GRNs remain largely undefined. We investigated networks controlled by the vital transcription factor MEF2C using a time course of single-nucleus RNA sequencing and ATAC sequencing in wild-type and Mef2c -null embryos. We identified a “posteriorized” cardiac gene signature and chromatin landscape in the absence of MEF2C. Integrating our multiomics data in a deep learning-based model, we constructed developmental trajectories for each of the outflow tract, ventricular, and inflow tract segments and alterations of these in Mef2c -null embryos. We computationally identified segment-specific MEF2C-dependent enhancers with activity in the developing zebrafish heart. Finally, using inferred GRNs, we discovered that the Mef2c -null heart malformations are partly driven by increased activity of the nuclear hormone receptor NR2F2. Our results delineate lineage-specific GRNs in the early heart tube and provide a generalizable framework for dissecting transcriptional networks governing developmental processes.","journal":"Genes & Development","year":2025,"id":555036,"datarank":0.33013632699628676,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.06137240661207849,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.06137240661207849,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":4,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE280587"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":316846,"name":"Tanvi Sinha","orcid":"0000-0001-9509-5687","position":1,"is_corresponding":false},{"id":829939,"name":"Alexander P. Clark","orcid":"0000-0002-5200-6573","position":2,"is_corresponding":false},{"id":1328414,"name":"Emily F. Brower","orcid":null,"position":3,"is_corresponding":false},{"id":329730,"name":"Jeffrey J. Saucerman","orcid":"0000-0001-9464-8374","position":4,"is_corresponding":false},{"id":316851,"name":"Brian L. Black","orcid":"0000-0002-6664-8913","position":5,"is_corresponding":false},{"id":44510,"name":"Benoit G. Bruneau","orcid":"0000-0002-0804-7597","position":6,"is_corresponding":false},{"id":259829,"name":"Jonathon M. Muncie","orcid":"0000-0002-7405-6213","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:54:54.542303Z","pmid":"40883017","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":[]}