{"doi":"10.1101/2022.08.02.502490","title":"Prevalent regulation of GATA2/3 and MSX2 on endogenous retrovirus-derived regulatory elements in human trophoblast stem cells","abstract":"Abstract The placenta is an organ with extraordinary phenotypic diversity in eutherian mammals. Recent evidence suggests that numerous human placental enhancers are evolved from lineage-specific insertions of endogenous retroviruses (ERVs), yet the transcription factors (TFs) underlying their regulation remain largely elusive. Here, by first focusing on MER41, a primate-specific ERV family previously linked to placenta and innate immunity, we uncover the binding motifs of multiple crucial trophoblast TFs (GATA2/3, MSX2, GRHL2) in addition to innate immunity TFs STAT1 and IRF1. Integration of ChIP-Seq data confirms the binding of GATA2/3, MSX2 and their related factors on the majority of MER41-derived enhancers in human trophoblast stem cells (TSCs). Notably, MER41-derived enhancers that are constitutively active in human TSCs are distinct from those activated upon interferon stimulation, which is determined by the binding of relevant TFs and their sub-family compositions. We further demonstrate that GATA2/3 and MSX2 have prevalent binding on numerous other ERV families – indicating their broad impact on ERV-derived enhancers. Functionally, the derepression of many syncytiotrophoblast genes after disruption of MSX2 is likely to be mediated by regulatory elements derived from ERVs – suggesting ERVs are also important for mediating transcriptional repression. Overall, this study characterized the prevalent regulation of GATA2/3, MSX2 and their co-factors on ERV-derived regulatory elements in human TSCs and provided mechanistic insights into the importance of ERVs in human trophoblast regulatory network.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303976,"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":0.9504,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":257821,"name":"Jing Jiang","orcid":"0000-0003-2042-7522","position":1,"is_corresponding":false},{"id":996827,"name":"Yuzhuo Li","orcid":null,"position":2,"is_corresponding":false},{"id":996394,"name":"Miao Yu","orcid":"0009-0004-1419-0818","position":3,"is_corresponding":false},{"id":996395,"name":"Jian Jin","orcid":"0000-0002-1034-5710","position":4,"is_corresponding":false},{"id":996396,"name":"Shuai Chen","orcid":"0000-0003-1280-018X","position":5,"is_corresponding":false},{"id":996397,"name":"Hairui Fan","orcid":"0000-0003-2472-4647","position":6,"is_corresponding":false},{"id":258781,"name":"Todd S. Macfarlan","orcid":"0000-0003-2495-9809","position":7,"is_corresponding":false},{"id":996398,"name":"Bin Cao","orcid":"0000-0003-2516-790X","position":8,"is_corresponding":false},{"id":264033,"name":"Ming‐an Sun","orcid":"0000-0002-4661-3027","position":9,"is_corresponding":false},{"id":996393,"name":"Cui Du","orcid":"0000-0002-3060-5698","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T00:32:28.468841Z","pmid":null,"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":[]}