| 1. |
- Rentoft, Matilda, et al.
(författare)
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Enhancer requirement for histone methylation linked with gene activation
- 2008
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Ingår i: The FEBS Journal. - Malden : Wiley-Blackwell. - 1742-464X .- 1742-4658. ; 275:23, s. 5994-6001
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Tidskriftsartikel (refereegranskat)abstract
- Enhancers cause a high level of transcription and activation of chromatin structure at target genes. Hyperacetylation of histones H3 and H4, a mark of active chromatin, is established broadly across target loci by enhancers that function over long distances. In the present study, we studied the role of an enhancer in methylation of various lysine residues on H3 by comparing a model gene locus having an active enhancer with one in which the enhancer has been inactivated within the context of minichromosomes. The intact enhancer affected histone methylation at K4, K9 and K36 in distinct ways depending on the methylation level and the location in the locus. All three lysine residues were highly tri-methylated in the coding region of the gene linked to the active enhancer but not the inactive enhancer. However di-methylation of K9 and K36 was not affected by the enhancer. The enhancer region itself was marked by mono-methylation at K4 and K9, distinguishing it from the methyl marks in the gene coding region. These results indicate that an enhancer has roles in establishing active histone methylation patterns linked with gene transcription rather than removing methylation linked with gene inactivation.
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| 2. |
- Rentoft, Matilda, et al.
(författare)
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Gene expression profiling of archival tongue squamous cell carcinomas provides sub-classification based on DNA repair genes
- 2009
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 35:6, s. 1321-1330
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Tidskriftsartikel (refereegranskat)abstract
- A subgroup of patients with squamous cell carcinoma of the head and neck (SCCHN) comprise young persons under the age of 40, who have not been heavily exposed to the classical risk factors, smoking and alcohol. The number of SCCHN in young adults, particularly tongue tumours, is increasing in several parts of the world. Here we employed a novel gene expression array methodology specifically developed for analysis of degraded RNA and investigated the expression of 502 cancer-related genes in archival paraffin-embedded SCCHN of the tongue from young (< or =40) and elderly patients (> or =50). Genes detected as de-regulated in tumours compared to non-malignant controls were in concordance with results from earlier studies of fresh frozen material. No genes were detected as significantly differentially expressed between young and old patients suggesting that the overall pathobiology of SCCHN is similar in young and old. Unsupervised clustering divided tumours into three groups, irrespective of age, where several differentially expressed DNA repair genes were a prominent separation factor. High levels of DNA repair genes associated with impaired therapeutic response to radiation, suggesting that DNA repair genes play a role in clinical outcome after radiotherapy.
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