{"doi":"10.1093/g3journal/jkab428","title":"RNA sequencing-based screen for reactivation of silenced alleles of autosomal genes","abstract":"In mammalian cells, maternal and paternal alleles usually have similar transcriptional activity. Epigenetic mechanisms such as X-chromosome inactivation (XCI) and imprinting were historically viewed as rare exceptions to this rule. Discovery of autosomal monoallelic autosomal expression (MAE) a decade ago revealed an additional allele-specific mode regulating thousands of mammalian genes. Despite MAE prevalence, its mechanistic basis remains unknown. Using an RNA sequencing-based screen for reactivation of silenced alleles, we identified DNA methylation as key mechanism of MAE mitotic maintenance. In contrast with the all-or-nothing allelic choice in XCI, allele-specific expression in MAE loci is tunable, with exact allelic imbalance dependent on the extent of DNA methylation. In a subset of MAE genes, allelic imbalance was insensitive to DNA demethylation, implicating additional mechanisms in MAE maintenance in these loci. Our findings identify a key mechanism of MAE maintenance and provide basis for understanding the biological role of MAE.","journal":"G3 Genes Genomes Genetics","year":2021,"id":199592,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.948,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":17842,"name":"Denis L. J. Lafontaine","orcid":"0000-0001-7295-6288","position":1,"is_corresponding":false},{"id":11839,"name":"Sébastien Vigneau","orcid":"0000-0002-9091-2067","position":2,"is_corresponding":false},{"id":558512,"name":"Asia Mendelevich","orcid":"0000-0002-1221-3287","position":3,"is_corresponding":false},{"id":564310,"name":"S.V. Vinogradova","orcid":"0000-0002-5419-8812","position":4,"is_corresponding":false},{"id":558513,"name":"Kyomi J. Igarashi","orcid":"0000-0002-4352-3835","position":5,"is_corresponding":false},{"id":558514,"name":"Andrew N. Bortvin","orcid":"0000-0001-8784-6786","position":6,"is_corresponding":false},{"id":558515,"name":"Clara Pereira","orcid":"0000-0002-9519-2310","position":7,"is_corresponding":false},{"id":558516,"name":"Anwesha Nag","orcid":"0000-0002-1947-7429","position":8,"is_corresponding":false},{"id":558517,"name":"Alexander A. Gimelbrant","orcid":"0000-0001-6986-0285","position":9,"is_corresponding":false},{"id":558510,"name":"Saumya Gupta","orcid":"0000-0001-7703-918X","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-18T23:50:40.558460Z","pmid":"35100361","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":[]}