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dc.contributor.authorSloane, MA
dc.contributor.authorHesson, LB
dc.contributor.authorNunez, AC
dc.contributor.authorThompson, BA
dc.contributor.authorWard, RL
dc.date.accessioned2021-02-03T23:37:56Z
dc.date.available2021-02-03T23:37:56Z
dc.date.issued2014-12-13
dc.identifierpii: 32
dc.identifier.citationSloane, M. A., Hesson, L. B., Nunez, A. C., Thompson, B. A. & Ward, R. L. (2014). Nucleosome positioning is unaltered at MLH1 splice site mutations in cells derived from Lynch syndrome patients. CLINICAL EPIGENETICS, 6 (1), https://doi.org/10.1186/s13148-014-0032-6.
dc.identifier.issn1868-7083
dc.identifier.urihttp://hdl.handle.net/11343/258934
dc.description.abstractBACKGROUND: Splicing is more efficient when coupled with transcription and it has been proposed that nucleosomes enriched in exons are important for splice site recognition. Lynch syndrome is a familial cancer syndrome that can be caused by the autosomal dominant inheritance of splice site mutations in the MutL homolog 1 (MLH1) gene. To better understand the role of nucleosomes in splicing, we used MLH1 splice site mutations in Lynch syndrome cases as a model to investigate if abnormal splicing was associated with altered nucleosome positioning at exon-intron boundaries. FINDINGS: Nucleosome Occupancy and Methylome sequencing (NOMe-seq) was used to determine the allele-specific positioning of nucleosomes around heterozygous splice site mutations in lymphoblastoid cells lines (LCLs) derived from six Lynch syndrome patients. These mutations were previously shown to cause exon skipping in five of the six patients. Allele-specific high-resolution nucleosome mapping across exons and exon-intron boundaries revealed high levels of nucleosomes across all regions examined. Alleles containing donor or acceptor splice site mutations showed no consistent alteration in nucleosome positioning or occupancy. CONCLUSION: Nucleosomes were enriched at MLH1 exons in LCLs derived from Lynch syndrome patients, and in this model system the positioning of nucleosomes was unaltered at exon-intron boundaries containing splice site mutations. Thus, these splice site mutations alone do not significantly change the local organisation of nucleosomes.
dc.languageEnglish
dc.publisherBIOMED CENTRAL LTD
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleNucleosome positioning is unaltered at MLH1 splice site mutations in cells derived from Lynch syndrome patients
dc.typeJournal Article
dc.identifier.doi10.1186/s13148-014-0032-6
melbourne.affiliation.departmentClinical Pathology
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleClinical Epigenetics
melbourne.source.volume6
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1196759
melbourne.contributor.authorThompson, Bryony
dc.identifier.eissn1868-7083
melbourne.accessrightsOpen Access


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