{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:09:33Z","timestamp":1740146973191,"version":"3.37.3"},"reference-count":91,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GGP17006"],"award-info":[{"award-number":["GGP17006"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Familial Dysautonomia (FD) is a rare disease caused by ELP1 exon 20 skipping. Here we clarify the role of RNA Polymerase II (RNAPII) and chromatin on this splicing event. A slow RNAPII mutant and chromatin-modifying chemicals that reduce the rate of RNAPII elongation induce exon skipping whereas chemicals that create a more relaxed chromatin exon inclusion. In the brain of a mouse transgenic for the human FD-ELP1 we observed on this gene an age-dependent decrease in the RNAPII density profile that was most pronounced on the alternative exon, a robust increase in the repressive marks H3K27me3 and H3K9me3 and a decrease of H3K27Ac, together with a progressive reduction in ELP1 exon 20 inclusion level. In HEK 293T cells, selective drug-induced demethylation of H3K27 increased RNAPII elongation on ELP1 and SMN2, promoted the inclusion of the corresponding alternative exons, and, by RNA-sequencing analysis, induced changes in several alternative splicing events. These data suggest a co-transcriptional model of splicing regulation in which age-dependent changes in H3K27me3\/Ac modify the rate of RNAPII elongation and affect processing of ELP1 alternative exon 20.<\/jats:p>","DOI":"10.1371\/journal.pone.0298965","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T17:25:44Z","timestamp":1717435544000},"page":"e0298965","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age-dependent regulation of ELP1 exon 20 splicing in Familial Dysautonomia by RNA Polymerase II kinetics and chromatin structure"],"prefix":"10.1371","volume":"19","author":[{"given":"Federico","family":"Riccardi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0356-4947","authenticated-orcid":true,"given":"Giulia","family":"Romano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danilo","family":"Licastro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2678-3459","authenticated-orcid":true,"given":"Franco","family":"Pagani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"key":"pone.0298965.ref001","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nrg1451","article-title":"How did alternative splicing evolve?","volume":"5","author":"G Ast","year":"2004","journal-title":"Nat Rev Genet"},{"key":"pone.0298965.ref002","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nrm.2017.27","article-title":"Alternative splicing as a regulator of development and tissue identity","volume":"18","author":"FE Baralle","year":"2017","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pone.0298965.ref003","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1146\/annurev-biochem-060614-034242","article-title":"Regulation of Alternative Splicing Through Coupling with Transcription and Chromatin Structure","volume":"84","author":"S Naftelberg","year":"2015","journal-title":"Annu Rev Biochem"},{"key":"pone.0298965.ref004","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrm3742","article-title":"A day in the life of the spliceosome","volume":"15","author":"AG Matera","year":"2014","journal-title":"Nat Rev Mol Cell 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Yano","year":"2010","journal-title":"Neuron"},{"key":"pone.0298965.ref030","first-page":"186","article-title":"The giant protein titin as an integrator of myocyte signaling pathways","volume":"25","author":"WA Linke","year":"2010","journal-title":"Physiology (Bethesda)"},{"key":"pone.0298965.ref031","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/nm.2693","article-title":"RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing","volume":"18","author":"W Guo","year":"2012","journal-title":"Nat Med"},{"key":"pone.0298965.ref032","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1093\/nar\/gks1362","article-title":"Rbm20 regulates titin alternative splicing as a splicing repressor","volume":"41","author":"S Li","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"pone.0298965.ref033","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1083\/jcb.201206146","article-title":"Rbfox3-regulated alternative splicing of Numb promotes neuronal differentiation during development","volume":"200","author":"KK Kim","year":"2013","journal-title":"J Cell Biol"},{"key":"pone.0298965.ref034","doi-asserted-by":"crossref","first-page":"8768","DOI":"10.1038\/ncomms9768","article-title":"ESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation","volume":"6","author":"A Bhate","year":"2015","journal-title":"Nat Commun"},{"key":"pone.0298965.ref035","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/nature08911","article-title":"Chromatin remodelling during development","volume":"463","author":"L Ho","year":"2010","journal-title":"Nature"},{"key":"pone.0298965.ref036","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1242\/dev.128892","article-title":"ATP-dependent chromatin remodeling during mammalian development","volume":"143","author":"SK Hota","year":"2016","journal-title":"Development"},{"key":"pone.0298965.ref037","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2017.00243","article-title":"Chromatin Remodeling BAF (SWI\/SNF) Complexes in Neural Development and Disorders","volume":"10","author":"G Sokpor","year":"2017","journal-title":"Frontiers in Molecular Neuroscience"},{"key":"pone.0298965.ref038","doi-asserted-by":"crossref","first-page":"R147","DOI":"10.1530\/REP-17-0488","article-title":"Chromatin remodeling in mammalian embryos","volume":"155","author":"B Cabot","year":"2018","journal-title":"Reproduction"},{"key":"pone.0298965.ref039","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1542\/peds.3.4.468","article-title":"Central autonomic dysfunction with defective lacrimation; report of five cases","volume":"3","author":"CM Riley","year":"1949","journal-title":"Pediatrics"},{"key":"pone.0298965.ref040","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.pneurobio.2016.06.003","article-title":"Familial dysautonomia: History, genotype, phenotype and translational research","volume":"152","author":"L Norcliffe-Kaufmann","year":"2017","journal-title":"Progress in Neurobiology"},{"key":"pone.0298965.ref041","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1242\/dev.107797","article-title":"A neuron autonomous role for the familial dysautonomia gene ELP1 in sympathetic and sensory target tissue innervation","volume":"141","author":"MZ Jackson","year":"2014","journal-title":"Development"},{"key":"pone.0298965.ref042","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/humu.20401","article-title":"Weak definition of IKBKAP exon 20 leads to aberrant splicing in familial dysautonomia","volume":"28","author":"EC Ibrahim","year":"2007","journal-title":"Hum Mutat"},{"key":"pone.0298965.ref043","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.ygeno.2007.05.012","article-title":"A humanized IKBKAP transgenic mouse models a tissue-specific human splicing defect","volume":"90","author":"MM Hims","year":"2007","journal-title":"Genomics"},{"key":"pone.0298965.ref044","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1590\/1678-4685-gmb-2015-0335","article-title":"Familial Dysautonomia: Mechanisms and Models","volume":"39","author":"P Dietrich","year":"2016","journal-title":"Genet Mol Biol"},{"key":"pone.0298965.ref045","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1093\/nar\/gky249","article-title":"Antisense oligonucleotides correct the familial dysautonomia splicing defect in IKBKAP transgenic mice","volume":"46","author":"R Sinha","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"pone.0298965.ref046","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1093\/hmg\/ddy151","article-title":"Exon-specific U1 snRNAs improve ELP1 exon 20 definition and rescue ELP1 protein expression in a familial dysautonomia mouse model","volume":"27","author":"I Donadon","year":"2018","journal-title":"Human Molecular Genetics"},{"key":"pone.0298965.ref047","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1016\/j.ajhg.2022.07.004","article-title":"Rescue of a familial dysautonomia mouse model by AAV9-Exon-specific U1 snRNA","volume":"109","author":"G Romano","year":"2022","journal-title":"The American Journal of Human Genetics"},{"key":"pone.0298965.ref048","doi-asserted-by":"crossref","first-page":"4507","DOI":"10.1038\/s41467-021-24705-5","article-title":"Therapeutic manipulation of IKBKAP mis-splicing with a small molecule to cure familial dysautonomia","volume":"12","author":"M Ajiro","year":"2021","journal-title":"Nat Commun"},{"key":"pone.0298965.ref049","doi-asserted-by":"crossref","first-page":"3332","DOI":"10.1038\/s41467-021-23663-2","article-title":"A deep learning approach to identify gene targets of a therapeutic for human splicing disorders","volume":"12","author":"D Gao","year":"2021","journal-title":"Nat Commun"},{"key":"pone.0298965.ref050","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.ajhg.2019.02.009","article-title":"ELP1 Splicing Correction Reverses Proprioceptive Sensory Loss in Familial Dysautonomia","volume":"104","author":"E Morini","year":"2019","journal-title":"Am J Hum Genet"},{"key":"pone.0298965.ref051","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1093\/hmg\/ddh046","article-title":"Rescue of a human mRNA splicing defect by the plant cytokinin kinetin","volume":"13","author":"SA Slaugenhaupt","year":"2004","journal-title":"Hum Mol Genet"},{"key":"pone.0298965.ref052","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/nsmb.1666","article-title":"Rates of in situ transcription and splicing in large human genes","volume":"16","author":"J Singh","year":"2009","journal-title":"Nat Struct Mol Biol"},{"key":"pone.0298965.ref053","doi-asserted-by":"crossref","first-page":"11.14.1","DOI":"10.1002\/0471250953.bi1114s51","article-title":"Mapping RNA-seq Reads with STAR","volume":"51","author":"A Dobin","year":"2015","journal-title":"Curr Protoc Bioinformatics"},{"key":"pone.0298965.ref054","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"key":"pone.0298965.ref055","doi-asserted-by":"crossref","first-page":"E5593","DOI":"10.1073\/pnas.1419161111","article-title":"rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-Seq data","volume":"111","author":"S Shen","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0298965.ref056","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.cell.2014.11.035","article-title":"A highly conserved program of neuronal microexons is misregulated in autistic brains","volume":"159","author":"M Irimia","year":"2014","journal-title":"Cell"},{"key":"pone.0298965.ref057","first-page":"240","article-title":"Dissecting the transcriptional functions of human DNA topoisomerase I by selective inhibitors: implications for physiological and therapeutic modulation of enzyme activity","volume":"1806","author":"G Capranico","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"pone.0298965.ref058","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1101\/gr.111070.110","article-title":"Global impact of RNA polymerase II elongation inhibition on alternative splicing regulation","volume":"21","author":"JY Ip","year":"2011","journal-title":"Genome Research"},{"key":"pone.0298965.ref059","doi-asserted-by":"crossref","first-page":"7527","DOI":"10.1093\/nar\/gkw585","article-title":"Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb","volume":"44","author":"AJ C Quaresma","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"pone.0298965.ref060","article-title":"Stress and the Emerging Roles of Chromatin Remodeling in Signal Integration and Stable Transmission of Reversible Phenotypes","volume":"11","author":"ICG Weaver","year":"2017","journal-title":"Front Behav Neurosci"},{"key":"pone.0298965.ref061","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.1242\/dev.037127","article-title":"CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing","volume":"136","author":"F Tie","year":"2009","journal-title":"Development"},{"key":"pone.0298965.ref062","doi-asserted-by":"crossref","first-page":"4958","DOI":"10.1093\/nar\/gkq244","article-title":"Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes","volume":"38","author":"D Pasini","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"pone.0298965.ref063","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nchembio.2304","article-title":"An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED","volume":"13","author":"W Qi","year":"2017","journal-title":"Nat Chem Biol"},{"key":"pone.0298965.ref064","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1038\/s41467-019-09624-w","article-title":"Dissecting the role of H3K27 acetylation and methylation in PRC2 mediated control of cellular identity","volume":"10","author":"E Lavarone","year":"2019","journal-title":"Nat Commun"},{"key":"pone.0298965.ref065","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1093\/emboj\/20.7.1774","article-title":"Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping","volume":"20","author":"E Buratti","year":"2001","journal-title":"EMBO J"},{"key":"pone.0298965.ref066","doi-asserted-by":"crossref","first-page":"e1006082","DOI":"10.1371\/journal.pgen.1006082","article-title":"Molecular Basis and Therapeutic Strategies to Rescue Factor IX Variants That Affect Splicing and Protein Function","volume":"12","author":"M Tajnik","year":"2016","journal-title":"PLoS Genet"},{"key":"pone.0298965.ref067","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/nsmb.1821","article-title":"Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa","volume":"17","author":"U Brykczynska","year":"2010","journal-title":"Nat Struct Mol Biol"},{"key":"pone.0298965.ref068","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1101\/gad.308536.117","article-title":"Transcription factor-dependent \u2018anti-repressive\u2019 mammalian enhancers exclude H3K27me3 from extended genomic domains","volume":"31","author":"M Saxena","year":"2017","journal-title":"Genes Dev"},{"key":"pone.0298965.ref069","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.molcel.2020.01.017","article-title":"Replicational Dilution of H3K27me3 in Mammalian Cells and the Role of Poised Promoters","volume":"78","author":"U Jadhav","year":"2020","journal-title":"Molecular Cell"},{"key":"pone.0298965.ref070","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/s41467-021-20979-x","article-title":"Splicing-associated chromatin signatures: a combinatorial and position-dependent role for histone marks in splicing definition","volume":"12","author":"E Agirre","year":"2021","journal-title":"Nat Commun"},{"key":"pone.0298965.ref071","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s13059-018-1512-3","article-title":"Alternative splicing links histone modifications to stem cell fate decision","volume":"19","author":"Y Xu","year":"2018","journal-title":"Genome Biol"},{"key":"pone.0298965.ref072","doi-asserted-by":"crossref","first-page":"e1003611","DOI":"10.1371\/journal.pcbi.1003611","article-title":"Histone modifications are associated with transcript isoform diversity in normal and cancer cells","volume":"10","author":"O Podlaha","year":"2014","journal-title":"PLoS Comput Biol"},{"key":"pone.0298965.ref073","doi-asserted-by":"crossref","first-page":"7938","DOI":"10.1093\/nar\/gky395","article-title":"Blocking of an intronic splicing silencer completely rescues IKBKAP exon 20 splicing in familial dysautonomia patient cells","volume":"46","author":"GH Bruun","year":"2018","journal-title":"Nucleic Acids Research"},{"key":"pone.0298965.ref074","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nrc2736","article-title":"Polycomb group proteins: navigators of lineage pathways led astray in cancer","volume":"9","author":"AP Bracken","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"pone.0298965.ref075","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1093\/ilar.53.3-4.232","article-title":"Recruitment and biological consequences of histone modification of H3K27me3 and H3K9me3","volume":"53","author":"J Kim","year":"2012","journal-title":"ILAR J"},{"key":"pone.0298965.ref076","doi-asserted-by":"crossref","first-page":"16690","DOI":"10.1073\/pnas.0506955102","article-title":"Age-related changes of nuclear architecture in Caenorhabditis elegans","volume":"102","author":"E Haithcock","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0298965.ref077","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1126\/science.1127168","article-title":"Lamin A-dependent nuclear defects in human aging","volume":"312","author":"P Scaffidi","year":"2006","journal-title":"Science"},{"key":"pone.0298965.ref078","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/j.1474-9726.2008.00406.x","article-title":"The farnesylated nuclear proteins KUGELKERN and LAMIN B promote aging-like phenotypes in Drosophila flies","volume":"7","author":"A Brandt","year":"2008","journal-title":"Aging Cell"},{"key":"pone.0298965.ref079","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature20603","article-title":"Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals","volume":"540","author":"S Schw\u00f6rer","year":"2016","journal-title":"Nature"},{"key":"pone.0298965.ref080","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.cell.2006.02.043","article-title":"Control of developmental regulators by Polycomb in human embryonic stem cells","volume":"125","author":"TI Lee","year":"2006","journal-title":"Cell"},{"key":"pone.0298965.ref081","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.cell.2018.03.079","article-title":"Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging","volume":"173","author":"P Cheung","year":"2018","journal-title":"Cell"},{"key":"pone.0298965.ref082","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.bbagrm.2012.09.003","article-title":"RNA polymerase II transcription: Structure and mechanism","volume":"1829","author":"X Liu","year":"2013","journal-title":"Biochimica et Biophysica Acta (BBA)\u2014Gene Regulatory Mechanisms"},{"key":"pone.0298965.ref083","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1089\/scd.2008.0189","article-title":"Histone H3 modifications associated with differentiation and long-term culture of mesenchymal adipose stem cells","volume":"18","author":"A Noer","year":"2009","journal-title":"Stem Cells Dev"},{"key":"pone.0298965.ref084","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1111\/acel.12257","article-title":"RNA-seq of the aging brain in the short-lived fish N. furzeri\u2014conserved pathways and novel genes associated with neurogenesis","volume":"13","author":"M Baumgart","year":"2014","journal-title":"Aging Cell"},{"key":"pone.0298965.ref085","doi-asserted-by":"crossref","first-page":"E1169","DOI":"10.3390\/cells8101169","article-title":"Aging Triggers H3K27 Trimethylation Hoarding in the Chromatin of Nothobranchius furzeri Skeletal Muscle","volume":"8","author":"C Cencioni","year":"2019","journal-title":"Cells"},{"key":"pone.0298965.ref086","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s10522-009-9231-5","article-title":"Identification of histone methylation multiplicities patterns in the brain of senescence-accelerated prone mouse 8","volume":"11","author":"CM Wang","year":"2010","journal-title":"Biogerontology"},{"key":"pone.0298965.ref087","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1073\/pnas.0907739107","article-title":"Polycomb Repressive Complex 2 and Trithorax modulate Drosophila longevity and stress resistance","volume":"107","author":"AP Siebold","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0298965.ref088","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1111\/j.1474-9726.2011.00738.x","article-title":"The H3K27 demethylase UTX-1 regulates C. elegans lifespan in a germline-independent, insulin-dependent manner","volume":"10","author":"TJ Maures","year":"2011","journal-title":"Aging Cell"},{"key":"pone.0298965.ref089","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s13059-020-02115-y","article-title":"The RNA-binding protein SERBP1 functions as a novel oncogenic factor in glioblastoma by bridging cancer metabolism and epigenetic regulation","volume":"21","author":"A Kosti","year":"2020","journal-title":"Genome Biol"},{"key":"pone.0298965.ref090","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s13045-020-00937-8","article-title":"EZH2: a novel target for cancer treatment","volume":"13","author":"R Duan","year":"2020","journal-title":"J Hematol Oncol"},{"key":"pone.0298965.ref091","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.cell.2010.11.056","article-title":"Epigenetics in Alternative Pre-mRNA Splicing","volume":"144","author":"RF Luco","year":"2011","journal-title":"Cell"}],"container-title":["PLOS 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