{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:47:52Z","timestamp":1790628472487,"version":"4.1.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"7519","license":[{"start":{"date-parts":[[2014,7,27]],"date-time":"2014-07-27T00:00:00Z","timestamp":1406419200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2014,9]]},"DOI":"10.1038\/nature13575","type":"journal-article","created":{"date-parts":[[2014,7,25]],"date-time":"2014-07-25T10:13:11Z","timestamp":1406283191000},"page":"555-558","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":190,"title":["Antifungal drug resistance evoked via RNAi-dependent epimutations"],"prefix":"10.1038","volume":"513","author":[{"given":"Silvia","family":"Calo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecelia","family":"Shertz-Wall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Chan","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Bastidas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco E.","family":"Nicol\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A.","family":"Granek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Mieczkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Torres-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa M.","family":"Ruiz-V\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria E.","family":"Cardenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Heitman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,7,27]]},"reference":[{"key":"BFnature13575_CR1","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/0092-8674(91)90124-H","volume":"66","author":"J Liu","year":"1991","unstructured":"Liu, J. et al. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 66, 807\u2013815 (1991)","journal-title":"Cell"},{"key":"BFnature13575_CR2","doi-asserted-by":"publisher","first-page":"e1003625","DOI":"10.1371\/journal.ppat.1003625","volume":"9","author":"SC Lee","year":"2013","unstructured":"Lee, S. C., Li, A., Calo, S. & Heitman, J. Calcineurin plays key roles in the dimorphic transition and virulence of the human pathogenic zygomycete Mucor circinelloides . PLoS Pathog. 9, e1003625 (2013)","journal-title":"PLoS Pathog."},{"key":"BFnature13575_CR3","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1128\/MMBR.55.2.234-258.1991","volume":"55","author":"M Orlowski","year":"1991","unstructured":"Orlowski, M. Mucor dimorphism. Microbiol. Rev. 55, 234\u2013258 (1991)","journal-title":"Microbiol. Rev."},{"key":"BFnature13575_CR4","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1128\/EC.05284-11","volume":"11","author":"RJ Bastidas","year":"2012","unstructured":"Bastidas, R. J., Shertz, C. A., Lee, S. C., Heitman, J. & Cardenas, M. E. Rapamycin exerts antifungal activity in vitro and in vivo against Mucor circinelloides via FKBP12-dependent inhibition of Tor. Eukaryot. Cell 11, 270\u2013281 (2012)","journal-title":"Eukaryot. Cell"},{"key":"BFnature13575_CR5","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1126\/science.1715094","volume":"253","author":"J Heitman","year":"1991","unstructured":"Heitman, J., Movva, N. R. & Hall, M. N. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253, 905\u2013909 (1991)","journal-title":"Science"},{"key":"BFnature13575_CR6","doi-asserted-by":"publisher","first-page":"3983","DOI":"10.1093\/emboj\/cdg384","volume":"22","author":"FE Nicolas","year":"2003","unstructured":"Nicolas, F. E., Torres-Martinez, S. & Ruiz-Vazquez, R. M. Two classes of small antisense RNAs in fungal RNA silencing triggered by non-integrative transgenes. EMBO J. 22, 3983\u20133991 (2003)","journal-title":"EMBO J."},{"key":"BFnature13575_CR7","doi-asserted-by":"publisher","first-page":"5535","DOI":"10.1093\/nar\/gkq301","volume":"38","author":"FE Nicolas","year":"2010","unstructured":"Nicolas, F. E. et al. Endogenous short RNAs generated by Dicer 2 and RNA-dependent RNA polymerase 1 regulate mRNAs in the basal fungus Mucor circinelloides . Nucleic Acids Res. 38, 5535\u20135541 (2010)","journal-title":"Nucleic Acids Res."},{"key":"BFnature13575_CR8","doi-asserted-by":"publisher","first-page":"4451","DOI":"10.1002\/j.1460-2075.1992.tb05546.x","volume":"11","author":"L Rhounim","year":"1992","unstructured":"Rhounim, L., Rossignol, J. L. & Faugeron, G. Epimutation of repeated genes in Ascobolus immersus . EMBO J. 11, 4451\u20134457 (1992)","journal-title":"EMBO J."},{"key":"BFnature13575_CR9","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/S0092-8674(00)80161-0","volume":"86","author":"V Colot","year":"1996","unstructured":"Colot, V., Maloisel, L. & Rossignol, J. L. Interchromosomal transfer of epigenetic states in Ascobolus: transfer of DNA methylation is mechanistically related to homologous recombination. Cell 86, 855\u2013864 (1996)","journal-title":"Cell"},{"key":"BFnature13575_CR10","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/43657","volume":"401","author":"P Cubas","year":"1999","unstructured":"Cubas, P., Vincent, C. & Coen, E. An epigenetic mutation responsible for natural variation in floral symmetry. Nature 401, 157\u2013161 (1999)","journal-title":"Nature"},{"key":"BFnature13575_CR11","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/ng1342","volume":"36","author":"CM Suter","year":"2004","unstructured":"Suter, C. M., Martin, D. I. K. & Ward, R. L. Germline epimutation of MLH1 in individuals with multiple cancers. Nature Genet. 36, 497\u2013501 (2004)","journal-title":"Nature Genet."},{"key":"BFnature13575_CR12","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1038\/ng1866","volume":"38","author":"TL Chan","year":"2006","unstructured":"Chan, T. L. et al. Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer. Nature Genet. 38, 1178\u20131183 (2006)","journal-title":"Nature Genet."},{"key":"BFnature13575_CR13","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1056\/NEJMoa064522","volume":"356","author":"MP Hitchins","year":"2007","unstructured":"Hitchins, M. P. et al. Inheritance of a cancer-associated MLH1 germ-line epimutation. N. Engl. J. Med. 356, 697\u2013705 (2007)","journal-title":"N. Engl. J. Med."},{"key":"BFnature13575_CR14","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/BF00039378","volume":"32","author":"DC Baulcombe","year":"1996","unstructured":"Baulcombe, D. C. RNA as a target and an initiator of post-transcriptional gene silencing in transgenic plants. Plant Mol. Biol. 32, 79\u201388 (1996)","journal-title":"Plant Mol. Biol."},{"key":"BFnature13575_CR15","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1023\/A:1005946720438","volume":"37","author":"M Wassenegger","year":"1998","unstructured":"Wassenegger, M. & Pelissier, T. A model for RNA-mediated gene silencing in higher plants. Plant Mol. Biol. 37, 349\u2013362 (1998)","journal-title":"Plant Mol. Biol."},{"key":"BFnature13575_CR16","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1046\/j.1365-313X.1996.9060787.x","volume":"9","author":"T Elmayan","year":"1996","unstructured":"Elmayan, T. & Vaucheret, H. Expression of single copies of a strongly expressed 35S transgene can be silenced post-transcriptionally. Plant J. 9, 787\u2013797 (1996)","journal-title":"Plant J."},{"key":"BFnature13575_CR17","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1126\/science.1101092","volume":"306","author":"S Gazzani","year":"2004","unstructured":"Gazzani, S., Lawrenson, T., Woodward, C., Headon, D. & Sablowski, R. A link between mRNA turnover and RNA interference in Arabidopsis . Science 306, 1046\u20131048 (2004)","journal-title":"Science"},{"key":"BFnature13575_CR18","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1111\/j.1365-2958.2011.07939.x","volume":"83","author":"S Calo","year":"2012","unstructured":"Calo, S., Nicolas, F. E., Vila, A., Torres-Martinez, S. & Ruiz-Vazquez, R. M. Two distinct RNA-dependent RNA polymerases are required for initiation and amplification of RNA silencing in the basal fungus Mucor circinelloides . Mol. Microbiol. 83, 379\u2013394 (2012)","journal-title":"Mol. Microbiol."},{"key":"BFnature13575_CR19","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1128\/EC.00191-09","volume":"8","author":"JP de Haro","year":"2009","unstructured":"de Haro, J. P. et al. A single dicer gene is required for efficient gene silencing associated with two classes of small antisense RNAs in Mucor circinelloides . Eukaryot. Cell 8, 1486\u20131497 (2009)","journal-title":"Eukaryot. Cell"},{"key":"BFnature13575_CR20","doi-asserted-by":"publisher","first-page":"e69283","DOI":"10.1371\/journal.pone.0069283","volume":"8","author":"M Cervantes","year":"2013","unstructured":"Cervantes, M. et al. A single argonaute gene participates in exogenous and endogenous RNAi and controls cellular functions in the basal fungus Mucor circinelloides . PLoS ONE 8, e69283 (2013)","journal-title":"PLoS ONE"},{"key":"BFnature13575_CR21","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.fgb.2006.09.003","volume":"44","author":"FE Nicol\u00e1s","year":"2007","unstructured":"Nicol\u00e1s, F. E., de Haro, J. P., Torres-Martinez, S. & Ruiz-Vazquez, R. M. Mutants defective in a Mucor circinelloides dicer-like gene are not compromised in siRNA silencing but display developmental defects. Fungal Genet. Biol. 44, 504\u2013516 (2007)","journal-title":"Fungal Genet. Biol."},{"key":"BFnature13575_CR22","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/nature02302","volume":"427","author":"S Kennedy","year":"2004","unstructured":"Kennedy, S., Wang, D. & Ruvkun, G. A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans . Nature 427, 645\u2013649 (2004)","journal-title":"Nature"},{"key":"BFnature13575_CR23","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1002\/bies.20078","volume":"26","author":"L Timmons","year":"2004","unstructured":"Timmons, L. Endogenous inhibitors of RNA interference in Caenorhabditis elegans . Bioessays 26, 715\u2013718 (2004)","journal-title":"Bioessays"},{"key":"BFnature13575_CR24","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.molcel.2010.01.012","volume":"37","author":"JI Gent","year":"2010","unstructured":"Gent, J. I. et al. Distinct phases of siRNA synthesis in an endogenous RNAi pathway in C. elegans soma. Mol. Cell 37, 679\u2013689 (2010)","journal-title":"Mol. Cell"},{"key":"BFnature13575_CR25","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.gde.2011.12.004","volume":"22","author":"FE Reyes-Turcu","year":"2012","unstructured":"Reyes-Turcu, F. E. & Grewal, S. I. Different means, same end-heterochromatin formation by RNAi and RNAi-independent RNA processing factors in fission yeast. Curr. Opin. Genet. Dev. 22, 156\u2013163 (2012)","journal-title":"Curr. Opin. Genet. Dev."},{"key":"BFnature13575_CR26","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/nature11716","volume":"493","author":"S Yamanaka","year":"2013","unstructured":"Yamanaka, S. et al. RNAi triggered by specialized machinery silences developmental genes and retrotransposons. Nature 493, 557\u2013560 (2013)","journal-title":"Nature"},{"key":"BFnature13575_CR27","doi-asserted-by":"publisher","first-page":"e1002086","DOI":"10.1371\/journal.ppat.1002086","volume":"7","author":"CH Li","year":"2011","unstructured":"Li, C. H. et al. Sporangiospore size dimorphism is linked to virulence of Mucor circinelloides . PLoS Pathog. 7, e1002086 (2011)","journal-title":"PLoS Pathog."},{"key":"BFnature13575_CR28","first-page":"e01390","volume":"5","author":"SC Lee","year":"2014","unstructured":"Lee, S. C. et al. Analysis of a foodborne fungal pathogen outbreak: virulence and genome of a Mucor circinelloides isolate from yogurt. mBio 5, e01390\u201314 (2014)","journal-title":"mBio"},{"key":"BFnature13575_CR29","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1128\/JB.141.2.565-569.1980","volume":"141","author":"BA Lasker","year":"1980","unstructured":"Lasker, B. A. & Borgia, P. T. High-frequency heterokaryon formation by Mucor racemosus . J. Bacteriol. 141, 565\u2013569 (1980)","journal-title":"J. Bacteriol."},{"key":"BFnature13575_CR30","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1099\/mic.0.054106-0","volume":"158","author":"J Wetzel","year":"2012","unstructured":"Wetzel, J., Burmester, A., Kolbe, M. & Wostemeyer, J. The mating-related loci sexM and sexP of the zygomycetous fungus Mucor mucedo and their transcriptional regulation by trisporoid pheromones. Microbiology 158, 1016\u20131023 (2012)","journal-title":"Microbiology"},{"key":"BFnature13575_CR31","doi-asserted-by":"publisher","first-page":"15394","DOI":"10.1074\/jbc.M610366200","volume":"282","author":"L Murcia-Flores","year":"2007","unstructured":"Murcia-Flores, L., Lorca-Pascual, J. M., Garre, V., Torres-Martinez, S. & Ruiz-Vazquez, R. M. Non-AUG translation initiation of a fungal RING finger repressor involved in photocarotenogenesis. J. Biol. Chem. 282, 15394\u201315403 (2007)","journal-title":"J. Biol. Chem."},{"key":"BFnature13575_CR32","doi-asserted-by":"publisher","first-page":"5892","DOI":"10.1002\/j.1460-2075.1995.tb00277.x","volume":"14","author":"ME Cardenas","year":"1995","unstructured":"Cardenas, M. E. & Heitman, J. FKBP12-rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol-4 kinase activity. EMBO J. 14, 5892\u20135907 (1995)","journal-title":"EMBO J."},{"key":"BFnature13575_CR33","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.mimet.2011.01.002","volume":"84","author":"A Guti\u00e9rrez","year":"2011","unstructured":"Guti\u00e9rrez, A., Lopez-Garcia, S. & Garre, V. High reliability transformation of the basal fungus Mucor circinelloides by electroporation. J. Microbiol. Methods 84, 442\u2013446 (2011)","journal-title":"J. Microbiol. Methods"},{"key":"BFnature13575_CR34","doi-asserted-by":"publisher","first-page":"D26","DOI":"10.1093\/nar\/gkr947","volume":"40","author":"IV Grigoriev","year":"2012","unstructured":"Grigoriev, I. V. et al. The genome portal of the Department of Energy Joint Genome Institute. Nucleic Acids Res. 40, D26\u2013D32 (2012)","journal-title":"Nucleic Acids Res."},{"key":"BFnature13575_CR35","doi-asserted-by":"publisher","first-page":"R36","DOI":"10.1186\/gb-2013-14-4-r36","volume":"14","author":"D Kim","year":"2013","unstructured":"Kim, D. et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36 (2013)","journal-title":"Genome Biol."},{"key":"BFnature13575_CR36","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1101\/gr.849004","volume":"14","author":"GE Crooks","year":"2004","unstructured":"Crooks, G. E., Hon, G., Chandonia, J. M. & Brenner, S. E. WebLogo: a sequence logo generator. Genome Res. 14, 1188\u20131190 (2004)","journal-title":"Genome Res."},{"key":"BFnature13575_CR37","unstructured":"Heger, A. pysam: Python interface for the SAM\/BAM sequence alignment and mapping format. http:\/\/code.google.com\/p\/pysam\/ (2013)"},{"key":"BFnature13575_CR38","doi-asserted-by":"publisher","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","volume":"11","author":"S Anders","year":"2010","unstructured":"Anders, S. & Huber, W. Differential expression analysis for sequence count data. Genome Biol. 11, R106 (2010)","journal-title":"Genome Biol."},{"key":"BFnature13575_CR39","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1093\/bioinformatics\/btp163","volume":"25","author":"PJ Cock","year":"2009","unstructured":"Cock, P. J. et al. Biopython: freely available Python tools for computational molecular biology and bioinformatics. Bioinformatics 25, 1422\u20131423 (2009)","journal-title":"Bioinformatics"},{"key":"BFnature13575_CR40","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1109\/MCSE.2007.55","volume":"9","author":"JD Hunter","year":"2007","unstructured":"Hunter, J. D. Matplotlib: A 2D graphics environment. Comput. Sci. Eng. 9, 90\u201395 (2007)","journal-title":"Comput. Sci. Eng."},{"key":"BFnature13575_CR41","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1109\/MCSE.2007.58","volume":"9","author":"TE Oliphant","year":"2007","unstructured":"Oliphant, T. E. Python for scientific computing. Comput. Sci. Eng. 9, 10\u201320 (2007)","journal-title":"Comput. Sci. Eng."},{"key":"BFnature13575_CR42","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","volume":"30","author":"R Edgar","year":"2002","unstructured":"Edgar, R., Domrachev, M. & Lash, A. E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30, 207\u2013210 (2002)","journal-title":"Nucleic Acids Res."},{"key":"BFnature13575_CR43","doi-asserted-by":"crossref","unstructured":"Anders, S., Pyl, P. T. & Huber, W. HTSeq - A Python framework to work with high-throughput sequencing data. Preprint at http:\/\/biorxiv.org\/content\/early\/2014\/02\/20\/002824 (2014)","DOI":"10.1101\/002824"},{"key":"BFnature13575_CR44","volume-title":"R: A Language and Environment for Statistical Computing","author":"The R Development Core Team","year":"2013","unstructured":"The R Development Core Team R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2013)"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature13575.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature13575","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature13575.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T14:23:13Z","timestamp":1684419793000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature13575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,27]]},"references-count":44,"journal-issue":{"issue":"7519","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["BFnature13575"],"URL":"https:\/\/doi.org\/10.1038\/nature13575","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718513243.793498239","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.718513243.793502174","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.718513243.793498261","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,27]]},"assertion":[{"value":"19 September 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 2014","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2014","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}