{"doi":"10.1101/2024.04.26.591383","title":"Reduced Levels of Lagging Strand Polymerases Shape Stem Cell Chromatin","abstract":"Abstract Stem cells display asymmetric histone inheritance while non-stem progenitor cells exhibit symmetric patterns in the Drosophila male germline lineage. Here, we report that components involved in lagging strand synthesis, such as DNA polymerase α and δ (Polα and Polδ), have significantly reduced levels in stem cells compared to progenitor cells. Compromising Polα genetically induces the replication-coupled histone incorporation pattern in progenitor cells to be indistinguishable from that in stem cells, which can be recapitulated using a Polα inhibitor in a concentration-dependent manner. Furthermore, stem cell-derived chromatin fibers display a higher degree of old histone recycling by the leading strand compared to progenitor cell-derived chromatin fibers. However, upon reducing Polα levels in progenitor cells, the chromatin fibers now display asymmetric old histone recycling just like GSC-derived fibers. The old versus new histone asymmetry is comparable between stem cells and progenitor cells at both S-phase and M-phase. Together, these results indicate that developmentally programmed expression of key DNA replication components is important to shape stem cell chromatin. Furthermore, manipulating one crucial DNA replication component can induce replication-coupled histone dynamics in non-stem cells in a manner similar to that in stem cells. One Sentence Summary Delayed lagging strand synthesis regulates asymmetric histone incorporation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":490828,"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":0.9558,"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":1092618,"name":"Brendon E. M. Davis","orcid":"0000-0002-7672-5038","position":1,"is_corresponding":false},{"id":819935,"name":"Rajesh Ranjan","orcid":"0000-0003-1368-6067","position":2,"is_corresponding":false},{"id":302743,"name":"Matthew Wooten","orcid":"0000-0001-8629-9899","position":3,"is_corresponding":false},{"id":813029,"name":"Joshua Blundon","orcid":"0009-0009-8412-6818","position":4,"is_corresponding":false},{"id":463359,"name":"Xin Chen","orcid":"0000-0002-6990-0926","position":5,"is_corresponding":false},{"id":647988,"name":"Jonathan C. Snedeker","orcid":"0000-0002-0399-5459","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":null,"created_at":"2026-07-19T02:08:37.162700Z","pmid":"38746451","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":[]}