{"doi":"10.1101/gad.1422906","title":"Dosage compensation in mammals: fine-tuning the expression of the X chromosome","abstract":"<jats:p>Mammalian females have two X chromosomes and males have only one. This has led to the evolution of special mechanisms of dosage compensation. The inactivation of one X chromosome in females equalizes gene expression between the sexes. This process of X-chromosome inactivation (XCI) is a remarkable example of long-range, monoallelic gene silencing and facultative heterochromatin formation, and the questions surrounding it have fascinated biologists for decades. How does the inactivation of more than a thousand genes on one X chromosome take place while the other X chromosome, present in the same nucleus, remains genetically active? What are the underlying mechanisms that trigger the initial differential treatment of the two X chromosomes? How is this differential treatment maintained once it has been established, and how are some genes able to escape the process? Does the mechanism of X inactivation vary between species and even between lineages? In this review, X inactivation is considered in evolutionary terms, and we discuss recent insights into the epigenetic changes and developmental timing of this process. We also review the discovery and possible implications of a second form of dosage compensation in mammals that deals with the unique, potentially haploinsufficient, status of the X chromosome with respect to autosomal gene expression.</jats:p>","journal":"Genes &amp; Development","year":2006,"id":640922,"datarank":0.9389372196097386,"base_score":6.259581464064923,"endowment":6.259581464064923,"self_citation_contribution":0.9389372196097386,"citation_network_contribution":0.0,"self_endowment_contribution":0.9389372196097386,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":522,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":120725,"name":"Christine M. 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What are the underlying mechanisms that trigger the initial differential treatment of the two X chromosomes? How is this differential treatment maintained once it has been established, and how are some genes able to escape the process? Does the mechanism of X inactivation vary between species and even between lineages? In this review, X inactivation is considered in evolutionary terms, and we discuss recent insights into the epigenetic changes and developmental timing of this process. We also review the discovery and possible implications of a second form of dosage compensation in mammals that deals with the unique, potentially haploinsufficient, status of the X chromosome with respect to autosomal gene expression.</jats:p>","is_dataset_classified":null,"base_score":6.259581464064923,"endowment":6.259581464064923,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16847345","pmcid":null,"openalex_id":"https://openalex.org/W2140244319","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2012,"count":26},{"year":2013,"count":28},{"year":2014,"count":35},{"year":2015,"count":31},{"year":2016,"count":22},{"year":2017,"count":20},{"year":2018,"count":11},{"year":2019,"count":16},{"year":2020,"count":14},{"year":2021,"count":33},{"year":2022,"count":13},{"year":2023,"count":10},{"year":2024,"count":14},{"year":2025,"count":7},{"year":2026,"count":7}],"oa_status":"gold","license":null,"oa_locations":[{"url":"http://genesdev.cshlp.org/content/20/14/1848.full.pdf","host_type":"journal"},{"url":"http://genesdev.cshlp.org/content/20/14/1848.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1101/gad.1422906","host_type":"publisher"},{"url":"https://doi.org/10.1101/gad.1422906","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16847345","host_type":"repository"}],"fields_of_study":["Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities","Chromosomal and Genetic Variations","Genomics and Chromatin Dynamics"],"mesh_terms":["Amino Acid Sequence","Animals","Dosage Compensation, Genetic","Biological Evolution","Female","Male","Mammals","Molecular Sequence Data","Spermatogenesis","X Chromosome","Genomic Imprinting","Epigenesis, Genetic","X Chromosome Inactivation"],"keywords":["Dosage compensation","X-inactivation","Biology","Heterochromatin","X chromosome","Skewed X-inactivation","Genetics","XIST","Epigenetics","Haploinsufficiency","Gene","Chromosome","Gene silencing","Gene dosage","Gene expression","Evolutionary biology","Phenotype"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T14:26:42.133574Z","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":[]}