{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:21:46Z","timestamp":1790749306840,"version":"4.1.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,2,22]],"date-time":"2017-02-22T00:00:00Z","timestamp":1487721600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,2,22]],"date-time":"2017-02-22T00:00:00Z","timestamp":1487721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Epigenetic and transcriptional alterations are both implicated in Huntington\u2019s disease (HD), a progressive neurodegenerative disease resulting in degeneration of striatal neurons in the brain. However, how impaired epigenetic regulation leads to transcriptional dysregulation in HD is unclear. Here, we investigated enhancer RNAs (eRNAs), a class of long non-coding RNAs transcribed from active enhancers. We found that eRNAs are expressed from many enhancers of mouse striatum and showed that a subset of those eRNAs are deregulated in HD<jats:italic>vs<\/jats:italic>control mouse striatum. Enhancer regions producing eRNAs decreased in HD mouse striatum were associated with genes involved in striatal neuron identity. Consistently, they were enriched in striatal super-enhancers. Moreover, decreased eRNA expression in HD mouse striatum correlated with down-regulation of associated genes. Additionally, a significant number of RNA Polymerase II (RNAPII) binding sites were lost within enhancers associated with decreased eRNAs in HD<jats:italic>vs<\/jats:italic>control mouse striatum. Together, this indicates that loss of RNAPII at HD mouse enhancers contributes to reduced transcription of eRNAs, resulting in down-regulation of target genes. Thus, our data support the view that eRNA dysregulation in HD striatum is a key mechanism leading to altered transcription of striatal neuron identity genes, through reduced recruitment of RNAPII at super-enhancers.<\/jats:p>","DOI":"10.1038\/srep42875","type":"journal-article","created":{"date-parts":[[2017,2,22]],"date-time":"2017-02-22T10:10:17Z","timestamp":1487758217000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Altered enhancer transcription underlies Huntington\u2019s disease striatal transcriptional signature"],"prefix":"10.1038","volume":"7","author":[{"given":"St\u00e9phanie","family":"Le Gras","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Keime","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Anthony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Lotz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"De Longprez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Brouillet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Cassel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Laurence","family":"Boutillier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Merienne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,22]]},"reference":[{"key":"BFsrep42875_CR1","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.nbd.2011.07.001","volume":"45","author":"T Seredenina","year":"2012","unstructured":"Seredenina, T. & Luthi-Carter, R. What have we learned from gene expression profiles in Huntington\u2019s disease? Neurobiol Dis 45, 83\u201398, doi: 10.1016\/j.nbd.2011.07.001 (2012).","journal-title":"Neurobiol Dis"},{"key":"BFsrep42875_CR2","doi-asserted-by":"publisher","first-page":"3481","DOI":"10.1093\/hmg\/ddv099","volume":"24","author":"M Achour","year":"2015","unstructured":"Achour, M. et al. Neuronal identity genes regulated by super-enhancers are preferentially down-regulated in the striatum of Huntington\u2019s disease mice. Hum Mol Genet 24, 3481\u20133496, doi: 10.1093\/hmg\/ddv099 (2015).","journal-title":"Hum Mol Genet"},{"key":"BFsrep42875_CR3","doi-asserted-by":"publisher","first-page":"10471","DOI":"10.1523\/JNEUROSCI.0670-13.2013","volume":"33","author":"LM Valor","year":"2013","unstructured":"Valor, L. M., Guiretti, D., Lopez-Atalaya, J. P. & Barco, A. Genomic landscape of transcriptional and epigenetic dysregulation in early onset polyglutamine disease. J Neurosci 33, 10471\u201310482, doi: 10.1523\/JNEUROSCI.0670-13.2013 (2013).","journal-title":"J Neurosci"},{"key":"BFsrep42875_CR4","doi-asserted-by":"publisher","first-page":"E3027","DOI":"10.1073\/pnas.1311323110","volume":"110","author":"M Vashishtha","year":"2013","unstructured":"Vashishtha, M. et al. Targeting H3K4 trimethylation in Huntington disease. Proc Natl Acad Sci USA 110, E3027\u20133036, doi: 10.1073\/pnas.1311323110 (2013).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep42875_CR5","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1093\/hmg\/ddp524","volume":"19","author":"IS Seong","year":"2010","unstructured":"Seong, I. S. et al. Huntingtin facilitates polycomb repressive complex 2. Hum Mol Genet 19, 573\u2013583, doi: 10.1093\/hmg\/ddp524 (2010).","journal-title":"Hum Mol Genet"},{"key":"BFsrep42875_CR6","doi-asserted-by":"crossref","unstructured":"Biagioli, M. et al. Htt CAG repeat expansion confers pleiotropic gains of mutant huntingtin function in chromatin regulation. Hum Mol Genet, doi: 10.1093\/hmg\/ddv006 (2015).","DOI":"10.1093\/hmg\/ddv006"},{"key":"BFsrep42875_CR7","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1093\/hmg\/ddu561","volume":"24","author":"G Bai","year":"2015","unstructured":"Bai, G. et al. Epigenetic dysregulation of hairy and enhancer of split 4 (HES4) is associated with striatal degeneration in postmortem Huntington brains. Hum Mol Genet 24, 1441\u20131456, doi: 10.1093\/hmg\/ddu561 (2015).","journal-title":"Hum Mol Genet"},{"key":"BFsrep42875_CR8","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1093\/hmg\/ddl013","volume":"15","author":"A Hodges","year":"2006","unstructured":"Hodges, A. et al. Regional and cellular gene expression changes in human Huntington\u2019s disease brain. Hum Mol Genet 15, 965\u2013977, doi: 10.1093\/hmg\/ddl013 (2006).","journal-title":"Hum Mol Genet"},{"key":"BFsrep42875_CR9","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1093\/hmg\/ddm133","volume":"16","author":"A Kuhn","year":"2007","unstructured":"Kuhn, A. et al. Mutant huntingtin\u2019s effects on striatal gene expression in mice recapitulate changes observed in human Huntington\u2019s disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage. Hum Mol Genet 16, 1845\u20131861, doi: 10.1093\/hmg\/ddm133 (2007).","journal-title":"Hum Mol Genet"},{"key":"BFsrep42875_CR10","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/nn.4256","volume":"19","author":"P Langfelder","year":"2016","unstructured":"Langfelder, P. et al. Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice. Nat Neurosci 19, 623\u2013633, doi: 10.1038\/nn.4256 (2016).","journal-title":"Nat Neurosci"},{"key":"BFsrep42875_CR11","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1093\/hmg\/ddm133","volume":"16","author":"A Kuhn","year":"2007","unstructured":"Kuhn, A. et al. Mutant huntingtin\u2019s effects on striatal gene expression in mice recapitulate changes observed in human Huntington\u2019s disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage. Hum Mol Genet 16, 1845\u20131861 (2007).","journal-title":"Hum Mol Genet"},{"key":"BFsrep42875_CR12","doi-asserted-by":"publisher","first-page":"295","DOI":"10.3389\/fncel.2014.00295","volume":"8","author":"L Francelle","year":"2014","unstructured":"Francelle, L., Galvan, L. & Brouillet, E. Possible involvement of self-defense mechanisms in the preferential vulnerability of the striatum in Huntington\u2019s disease. Front Cell Neurosci 8, 295, doi: 10.3389\/fncel.2014.00295 (2014).","journal-title":"Front Cell Neurosci"},{"key":"BFsrep42875_CR13","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1093\/hmg\/9.9.1259","volume":"9","author":"R Luthi-Carter","year":"2000","unstructured":"Luthi-Carter, R. et al. Decreased expression of striatal signaling genes in a mouse model of Huntington\u2019s disease. Hum. Mol. Genet. 9, 1259\u20131271 (2000).","journal-title":"Hum. Mol. Genet"},{"key":"BFsrep42875_CR14","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1007\/s12035-014-8715-8","volume":"51","author":"LM Valor","year":"2015","unstructured":"Valor, L. M. Transcription, epigenetics and ameliorative strategies in Huntington\u2019s Disease: a genome-wide perspective. Mol Neurobiol 51, 406\u2013423, doi: 10.1007\/s12035-014-8715-8 (2015).","journal-title":"Mol Neurobiol"},{"key":"BFsrep42875_CR15","doi-asserted-by":"publisher","first-page":"e1004610","DOI":"10.1371\/journal.pgen.1004610","volume":"10","author":"H Wu","year":"2014","unstructured":"Wu, H. et al. Tissue-specific RNA expression marks distant-acting developmental enhancers. PLoS Genet 10, e1004610, doi: 10.1371\/journal.pgen.1004610 (2014).","journal-title":"PLoS Genet"},{"key":"BFsrep42875_CR16","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/nature09033","volume":"465","author":"TK Kim","year":"2010","unstructured":"Kim, T. K. et al. Widespread transcription at neuronal activity-regulated enhancers. Nature 465, 182\u2013187, doi: 10.1038\/nature09033 (2010).","journal-title":"Nature"},{"key":"BFsrep42875_CR17","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1038\/nn.3808","volume":"17","author":"AN Malik","year":"2014","unstructured":"Malik, A. N. et al. Genome-wide identification and characterization of functional neuronal activity-dependent enhancers. Nat Neurosci 17, 1330\u20131339, doi: 10.1038\/nn.3808 (2014).","journal-title":"Nat Neurosci"},{"key":"BFsrep42875_CR18","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1126\/science.1259418","volume":"347","author":"E Arner","year":"2015","unstructured":"Arner, E. et al. Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science 347, 1010\u20131014, doi: 10.1126\/science.1259418 (2015).","journal-title":"Science"},{"key":"BFsrep42875_CR19","doi-asserted-by":"publisher","first-page":"E297","DOI":"10.1073\/pnas.1424028112","volume":"112","author":"N Hah","year":"2015","unstructured":"Hah, N. et al. Inflammation-sensitive super enhancers form domains of coordinately regulated enhancer RNAs. Proc Natl Acad Sci USA 112, E297\u2013302, doi: 10.1073\/pnas.1424028112 (2015).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep42875_CR20","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.molcel.2014.08.023","volume":"56","author":"K Schaukowitch","year":"2014","unstructured":"Schaukowitch, K. et al. Enhancer RNA Facilitates NELF Release from Immediate Early Genes. Mol Cell 56, 29\u201342, doi: 10.1016\/j.molcel.2014.08.023 (2014).","journal-title":"Mol Cell"},{"key":"BFsrep42875_CR21","doi-asserted-by":"publisher","first-page":"4369","DOI":"10.1073\/pnas.1414841112","volume":"112","author":"L Pnueli","year":"2015","unstructured":"Pnueli, L., Rudnizky, S., Yosefzon, Y. & Melamed, P. RNA transcribed from a distal enhancer is required for activating the chromatin at the promoter of the gonadotropin alpha-subunit gene. Proc Natl Acad Sci USA 112, 4369\u20134374, doi: 10.1073\/pnas.1414841112 (2015).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep42875_CR22","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nbt.1630","volume":"28","author":"CY McLean","year":"2010","unstructured":"McLean, C. Y. et al. GREAT improves functional interpretation of cis-regulatory regions. Nature biotechnology 28, 495\u2013501, doi: 10.1038\/nbt.1630 (2010).","journal-title":"Nature biotechnology"},{"key":"BFsrep42875_CR23","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.brainres.2015.02.046","volume":"1608","author":"J Yuan","year":"2015","unstructured":"Yuan, J., Lei, Z. N., Wang, X., Deng, Y. J. & Chen, D. B. Interaction between Oc-1 and Lmx1a promotes ventral midbrain dopamine neural stem cells differentiation into dopamine neurons. Brain Res 1608, 40\u201350, doi: 10.1016\/j.brainres.2015.02.046 (2015).","journal-title":"Brain Res"},{"key":"BFsrep42875_CR24","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1152\/jn.00791.2004","volume":"93","author":"MA Ariano","year":"2005","unstructured":"Ariano, M. A. et al. Striatal potassium channel dysfunction in Huntington\u2019s disease transgenic mice. J Neurophysiol 93, 2565\u20132574, doi: 10.1152\/jn.00791.2004 (2005).","journal-title":"J Neurophysiol"},{"key":"BFsrep42875_CR25","doi-asserted-by":"publisher","first-page":"e1000384","DOI":"10.1371\/journal.pbio.1000384","volume":"8","author":"F De Santa","year":"2010","unstructured":"De Santa, F. et al. A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLoS Biol 8, e1000384, doi: 10.1371\/journal.pbio.1000384 (2010).","journal-title":"PLoS Biol"},{"key":"BFsrep42875_CR26","doi-asserted-by":"publisher","first-page":"67","DOI":"10.2217\/epi.11.112","volume":"4","author":"G Barkess","year":"2012","unstructured":"Barkess, G. & West, A. G. Chromatin insulator elements: establishing barriers to set heterochromatin boundaries. Epigenomics 4, 67\u201380, doi: 10.2217\/epi.11.112 (2012).","journal-title":"Epigenomics"},{"key":"BFsrep42875_CR27","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/1741-7007-8-125","volume":"8","author":"PY Bourillot","year":"2010","unstructured":"Bourillot, P. Y. & Savatier, P. Kruppel-like transcription factors and control of pluripotency. BMC Biol 8, 125, doi: 10.1186\/1741-7007-8-125 (2010).","journal-title":"BMC Biol"},{"key":"BFsrep42875_CR28","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/1741-7007-8-128","volume":"8","author":"S Parisi","year":"2010","unstructured":"Parisi, S. et al. Direct targets of Klf5 transcription factor contribute to the maintenance of mouse embryonic stem cell undifferentiated state. BMC Biol 8, 128, doi: 10.1186\/1741-7007-8-128 (2010).","journal-title":"BMC Biol"},{"key":"BFsrep42875_CR29","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1038\/nn1462","volume":"8","author":"N Ramanan","year":"2005","unstructured":"Ramanan, N. et al. SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability. Nat Neurosci 8, 759\u2013767, doi: 10.1038\/nn1462 (2005).","journal-title":"Nat Neurosci"},{"key":"BFsrep42875_CR30","doi-asserted-by":"publisher","first-page":"12648","DOI":"10.1038\/srep12648","volume":"5","author":"JH Cheng","year":"2015","unstructured":"Cheng, J. H., Pan, D. Z., Tsai, Z. T. & Tsai, H. K. Genome-wide analysis of enhancer RNA in gene regulation across 12 mouse tissues. Sci Rep 5, 12648, doi: 10.1038\/srep12648 (2015).","journal-title":"Sci Rep"},{"key":"BFsrep42875_CR31","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.neuron.2006.03.013","volume":"50","author":"A Etkin","year":"2006","unstructured":"Etkin, A. et al. A role in learning for SRF: deletion in the adult forebrain disrupts LTD and the formation of an immediate memory of a novel context. Neuron 50, 127\u2013143, doi: 10.1016\/j.neuron.2006.03.013 (2006).","journal-title":"Neuron"},{"key":"BFsrep42875_CR32","doi-asserted-by":"publisher","first-page":"2856","DOI":"10.1093\/hmg\/ddl224","volume":"15","author":"DM Cummings","year":"2006","unstructured":"Cummings, D. M. et al. Aberrant cortical synaptic plasticity and dopaminergic dysfunction in a mouse model of Huntington\u2019s disease. Hum Mol Genet 15, 2856\u20132868, doi: 10.1093\/hmg\/ddl224 (2006).","journal-title":"Hum Mol Genet"},{"key":"BFsrep42875_CR33","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1007\/BF00250260","volume":"72","author":"J Bargas","year":"1988","unstructured":"Bargas, J., Galarraga, E. & Aceves, J. Electrotonic properties of neostriatal neurons are modulated by extracellular potassium. Exp Brain Res 72, 390\u2013398 (1988).","journal-title":"Exp Brain Res"},{"key":"BFsrep42875_CR34","doi-asserted-by":"publisher","first-page":"6650","DOI":"10.1523\/JNEUROSCI.18-17-06650.1998","volume":"18","author":"PG Mermelstein","year":"1998","unstructured":"Mermelstein, P. G., Song, W. J., Tkatch, T., Yan, Z. & Surmeier, D. J. Inwardly rectifying potassium (IRK) currents are correlated with IRK subunit expression in rat nucleus accumbens medium spiny neurons. J Neurosci 18, 6650\u20136661 (1998).","journal-title":"J Neurosci"},{"key":"BFsrep42875_CR35","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1038\/nn.2900","volume":"14","author":"JU Guo","year":"2011","unstructured":"Guo, J. U. et al. Neuronal activity modifies the DNA methylation landscape in the adult brain. Nat Neurosci 14, 1345\u20131351, doi: 10.1038\/nn.2900 (2011).","journal-title":"Nat Neurosci"},{"key":"BFsrep42875_CR36","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1093\/nar\/gkv1332","volume":"44","author":"H Liu","year":"2016","unstructured":"Liu, H. et al. Systematic identification and annotation of human methylation marks based on bisulfite sequencing methylomes reveals distinct roles of cell type-specific hypomethylation in the regulation of cell identity genes. Nucleic Acids Res 44, 75\u201394, doi: 10.1093\/nar\/gkv1332 (2016).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep42875_CR37","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/S0092-8674(00)81369-0","volume":"87","author":"L Mangiarini","year":"1996","unstructured":"Mangiarini, L. et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87, 493\u2013506 (1996).","journal-title":"Cell"},{"key":"BFsrep42875_CR38","doi-asserted-by":"publisher","first-page":"1952","DOI":"10.1093\/bioinformatics\/btp340","volume":"25","author":"C Zang","year":"2009","unstructured":"Zang, C. et al. A clustering approach for identification of enriched domains from histone modification ChIP-Seq data. Bioinformatics 25, 1952\u20131958, doi: 10.1093\/bioinformatics\/btp340 (2009).","journal-title":"Bioinformatics"},{"key":"BFsrep42875_CR39","doi-asserted-by":"publisher","first-page":"R25","DOI":"10.1186\/gb-2009-10-3-r25","volume":"10","author":"B Langmead","year":"2009","unstructured":"Langmead, B., Trapnell, C., Pop, M. & Salzberg, S. L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10, R25, doi: 10.1186\/gb-2009-10-3-r25 (2009).","journal-title":"Genome Biol"},{"key":"BFsrep42875_CR40","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, doi: 10.1186\/gb-2013-14-4-r36 (2013).","journal-title":"Genome Biol"},{"key":"BFsrep42875_CR41","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1038\/nprot.2013.099","volume":"8","author":"S Anders","year":"2013","unstructured":"Anders, S. et al. Count-based differential expression analysis of RNA sequencing data using R and Bioconductor. Nat Protoc 8, 1765\u20131786, doi: 10.1038\/nprot.2013.099 (2013).","journal-title":"Nat Protoc"},{"key":"BFsrep42875_CR42","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, doi: 10.1186\/gb-2010-11-10-r106 (2010).","journal-title":"Genome Biol"},{"key":"BFsrep42875_CR43","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1101\/002832","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15, 550\u2013571, doi: 10.1101\/002832 (2014).","journal-title":"Genome Biol"},{"key":"BFsrep42875_CR44","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the False Discovery Rate - a Practical and Powerful Approach to Multiple Testing. J Roy Stat Soc B Met 57, 289\u2013300 (1995).","journal-title":"J Roy Stat Soc B Met"},{"key":"BFsrep42875_CR45","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","volume":"26","author":"AR Quinlan","year":"2010","unstructured":"Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841\u2013842, doi: 10.1093\/bioinformatics\/btq033 (2010).","journal-title":"Bioinformatics"},{"key":"BFsrep42875_CR46","doi-asserted-by":"publisher","first-page":"R137","DOI":"10.1186\/gb-2008-9-9-r137","volume":"9","author":"Y Zhang","year":"2008","unstructured":"Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol 9, R137, doi: 10.1186\/gb-2008-9-9-r137 (2008).","journal-title":"Genome Biol"},{"key":"BFsrep42875_CR47","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","volume":"38","author":"S Heinz","year":"2010","unstructured":"Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell 38, 576\u2013589, doi: 10.1016\/j.molcel.2010.05.004 (2010).","journal-title":"Mol Cell"},{"key":"BFsrep42875_CR48","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1093\/bioinformatics\/btr064","volume":"27","author":"CE Grant","year":"2011","unstructured":"Grant, C. E., Bailey, T. L. & Noble, W. S. FIMO: scanning for occurrences of a given motif. Bioinformatics 27, 1017\u20131018, doi: 10.1093\/bioinformatics\/btr064 (2011).","journal-title":"Bioinformatics"},{"key":"BFsrep42875_CR49","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","volume":"4","author":"W Huang da","year":"2009","unstructured":"Huang da, W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4, 44\u201357, doi: 10.1038\/nprot.2008.211 (2009).","journal-title":"Nat Protoc"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep42875.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep42875","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep42875.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T16:25:56Z","timestamp":1719073556000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep42875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,22]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,3,9]]}},"alternative-id":["BFsrep42875"],"URL":"https:\/\/doi.org\/10.1038\/srep42875","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,22]]},"assertion":[{"value":"2 August 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2017","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"}}],"article-number":"42875"}}