{"data":{"id":"10.6084/m9.figshare.1255029.v1","type":"dois","attributes":{"doi":"10.6084/m9.figshare.1255029.v1","prefix":"10.6084","suffix":"m9.figshare.1255029.v1","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Hesson, Luke B","nameType":"Personal","givenName":"Luke B","familyName":"Hesson","affiliation":[],"nameIdentifiers":[]},{"name":"Sloane, Mathew A","nameType":"Personal","givenName":"Mathew A","familyName":"Sloane","affiliation":[],"nameIdentifiers":[]},{"name":"Wong, Jason WH","nameType":"Personal","givenName":"Jason WH","familyName":"Wong","affiliation":[],"nameIdentifiers":[]},{"name":"Nunez, Andrea C","nameType":"Personal","givenName":"Andrea C","familyName":"Nunez","affiliation":[],"nameIdentifiers":[]},{"name":"Srivastava, Sameer","nameType":"Personal","givenName":"Sameer","familyName":"Srivastava","affiliation":[],"nameIdentifiers":[]},{"name":"Ng, Benedict","nameType":"Personal","givenName":"Benedict","familyName":"Ng","affiliation":[],"nameIdentifiers":[]},{"name":"Hawkins, Nicholas J","nameType":"Personal","givenName":"Nicholas J","familyName":"Hawkins","affiliation":[],"nameIdentifiers":[]},{"name":"Bourke, Michael J","nameType":"Personal","givenName":"Michael J","familyName":"Bourke","affiliation":[],"nameIdentifiers":[]},{"name":"Ward, Robyn L","nameType":"Personal","givenName":"Robyn L","familyName":"Ward","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Altered promoter nucleosome positioning is an early event in gene silencing"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2014,"subjects":[{"subject":"Computational Biology"},{"subject":"Biological Sciences"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Clinical medicine","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Meta Science"},{"subject":"Chemistry"},{"subject":"Physiology"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Biological sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Molecular Biology"},{"subject":"Genetics"},{"subject":"Cell Biology"},{"subject":"Medicine"}],"contributors":[],"dates":[{"date":"2014-10-03","dateType":"Created"},{"date":"2016-01-19","dateType":"Updated"},{"date":"2014","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.4161/15592294.2014.970077","relatedIdentifierType":"DOI"},{"relationType":"IsPreviousVersionOf","relatedIdentifier":"10.6084/m9.figshare.1255029","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["11822269 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"Gene silencing in cancer frequently involves hypermethylation and dense nucleosome occupancy across promoter regions. How a promoter transitions to this silent state is unclear. Using colorectal adenomas, we investigated nucleosome positioning, DNA methylation, and gene expression in the early stages of gene silencing. Genome-wide gene expression correlated with highly positioned nucleosomes upstream and downstream of a nucleosome-depleted transcription start site (TSS). Hypermethylated promoters displayed increased nucleosome occupancy, specifically at the TSS. We investigated 2 genes, \u003ci\u003eCDH1\u003c/i\u003e and \u003ci\u003eCDKN2B\u003c/i\u003e, which were silenced in adenomas but lacked promoter hypermethylation. Instead, silencing correlated with loss of nucleosomes from the -2 position upstream of the TSS relative to normal mucosa. In contrast, permanent \u003ci\u003eCDH1\u003c/i\u003e silencing in carcinoma cells was characterized by promoter hypermethylation and dense nucleosome occupancy. Our findings suggest that silenced genes transition through an intermediary stage involving altered promoter nucleosome positioning, before permanent silencing by hypermethylation and dense nucleosome occupancy.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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