{"doi":"10.1101/2024.03.18.585495","title":"14-3-3ζ regulates adipogenesis by modulating chromatin accessibility during the early stages of adipocyte differentiation","abstract":"ABSTRACT We previously established the scaffold protein 14-3-3ζ as a critical regulator of adipogenesis and adiposity, but the temporal specificity of its action during adipocyte differentiation remains unclear. To decipher if 14-3-3ζ exerts its regulatory functions on mature adipocytes or on adipose precursor cells (APCs), we generated Adipoq 14-3-3ζKO and Pdgfra 14-3-3ζKO mouse models. Our findings revealed a pivotal role for 14-3-3ζ in APC differentiation in a sex-dependent manner, whereby male and female Pdgfra 14-3-3ζKO mice display impaired or potentiated weight gain, respectively, as well as fat mass. To better understand how 14-3-3ζ regulates the adipogenic transcriptional program in APCs, CRISPR-Cas9 was used to generate TAP-tagged 14-3-3ζ-expressing 3T3-L1 preadipocytes. Using these cells, we examined if the 14-3-3ζ nuclear interactome is enriched with adipogenic regulators during differentiation. Regulators of chromatin remodeling, such as DNMT1 and HDAC1, were enriched in the nuclear interactome of 14-3-3ζ, and their activities were impacted upon 14-3-3ζ depletion. The interactions between 14-3-3ζ and chromatin-modifying enzymes suggested that 14-3-3ζ may control chromatin remodeling during adipogenesis, and this was confirmed by ATAC-seq, which revealed that 14-3-3ζ depletion impacted the accessibility of up to 1,244 chromatin regions corresponding in part to adipogenic genes, promoters, and enhancers during the initial stages of adipogenesis. Moreover, 14-3-3ζ-dependent chromatin accessibility was found to directly correlate with the expression of key adipogenic genes. Altogether, our study establishes 14-3-3ζ as a crucial epigenetic regulator of adipogenesis and highlights the usefulness of deciphering the nuclear 14-3-3ζ interactome to identify novel pro-adipogenic factors and pathways.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":490383,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9632,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":655822,"name":"Zhongsheng You","orcid":"0000-0002-9719-8791","position":1,"is_corresponding":false},{"id":828580,"name":"Alexis Vivoli","orcid":"0000-0002-6056-9632","position":2,"is_corresponding":false},{"id":1336032,"name":"Daphné Sean","orcid":null,"position":3,"is_corresponding":false},{"id":1336033,"name":"A. Alkhoury","orcid":null,"position":4,"is_corresponding":false},{"id":1335744,"name":"Gabriel Lavoie","orcid":"0009-0001-8339-1371","position":5,"is_corresponding":false},{"id":236714,"name":"Mete Civelek","orcid":"0000-0002-8141-0284","position":6,"is_corresponding":false},{"id":350914,"name":"Aida Martínez-Sánchez","orcid":"0000-0001-5142-2527","position":7,"is_corresponding":false},{"id":233594,"name":"Philippe P. Roux","orcid":"0000-0002-5962-0250","position":8,"is_corresponding":false},{"id":696324,"name":"Thomas M. Durcan","orcid":"0000-0003-3942-1956","position":9,"is_corresponding":false},{"id":823018,"name":"GE Lim","orcid":null,"position":10,"is_corresponding":false},{"id":1336031,"name":"SA Rial","orcid":null,"position":0,"is_corresponding":true}],"reference_count":122,"raw_metadata":null,"created_at":"2026-07-19T02:08:37.162700Z","pmid":"38562727","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":[]}