{"doi":"10.1101/2022.10.27.514094","title":"Equalizing epigenetically imprinted centromeres in early mammalian embryos","abstract":"Summary The CENP-A histone variant epigenetically defines centromeres, where its levels and locations are precisely maintained through mitotic cell divisions. However, differences in centromere CENP-A propagation in soma versus female/male germline remains poorly understood. Here, we generated C enpa mScarlet mice and followed CENP-A dynamics in gametes, zygotes, and embryos. We found that, unlike somatic cells, progenitor female and male germ cells carry high centromeric CENP-A levels that decrease upon terminal differentiation. The reduction in CENP-A is differentially regulated between sexes, resulting in a ten-fold higher level in oocytes compared to sperm. In the zygote, the parent-of-origin CENP-A asymmetry is equalized prior to initial S-phase by redistribution of nuclear CENP-A from maternal to paternal chromosomes. Redistribution of CENP-A requires both CDK1/2 and PLK1 centromeric machinery. These experiments provide direct evidence for resetting of epigenetically imprinted centromeres in early pronuclear stage embryos and imply a mechanism to sense the non-equivalency of parental chromosomes. Highlights Increased CENP-A density at centromeres is a conserved property of germline stem cells while CENP-A reduction is coincident with germ cell differentiation Paternal and maternal CENP-A containing nucleosomes are intergenerationally inherited CENP-A density at centromeres differs between male and female mature gametes Upon fertilization, maternal nuclear CENP-A is redistributed to equalize with parental CENP-A CENP-C and MIS18BP1 are asymmetrically enriched in the parental pronuclei in accordance with CENP-A asymmetry. Licensing for centromere equalization begins before zygotic DNA replication","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":298897,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9457,"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":806509,"name":"Kelsey Jorgensen","orcid":"0000-0002-8681-5248","position":1,"is_corresponding":false},{"id":391991,"name":"Bin Ma","orcid":"0009-0003-1048-4459","position":2,"is_corresponding":false},{"id":719640,"name":"Mansour Aboelenain","orcid":"0000-0002-3806-6748","position":3,"is_corresponding":false},{"id":988822,"name":"Catherine Tower","orcid":null,"position":4,"is_corresponding":false},{"id":988306,"name":"Saikat Chakraborty","orcid":"0000-0002-2908-7205","position":5,"is_corresponding":false},{"id":819935,"name":"Rajesh Ranjan","orcid":"0000-0003-1368-6067","position":6,"is_corresponding":false},{"id":719117,"name":"Arunika Das","orcid":"0000-0001-7116-3489","position":7,"is_corresponding":false},{"id":270406,"name":"Michael A. Lampson","orcid":"0000-0002-2825-1894","position":8,"is_corresponding":false},{"id":232713,"name":"Ben E. Black","orcid":"0000-0002-3707-9483","position":9,"is_corresponding":false},{"id":298427,"name":"Karen Schindler","orcid":"0000-0001-6113-1184","position":10,"is_corresponding":false},{"id":463359,"name":"Xin Chen","orcid":"0000-0002-6990-0926","position":11,"is_corresponding":false},{"id":235835,"name":"Saher Sue Hammoud","orcid":"0000-0002-5040-6370","position":12,"is_corresponding":false},{"id":235830,"name":"Gabriel Manske","orcid":"0000-0001-5461-4647","position":0,"is_corresponding":true}],"reference_count":107,"raw_metadata":null,"created_at":"2026-07-19T00:31:40.528568Z","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":[]}