Promoter analysis of epigenetically controlled genes in bladder cancer.
Veerla, Srinivas LU
; Panagopoulos, Ioannis
LU
; Jin, Yuesheng
LU
; Lindgren, David
LU
and Höglund, Mattias
LU
(2008)
In Genes, Chromosomes and Cancer
47.
p.368-378
- Abstract
- DNA methylation is an important epigenetic modification that regulates several genes crucial for tumor development. To identify epigenetically regulated genes in bladder cancer, we performed genome wide expression analyses of eight-bladder cancer cell lines treated with the demethylating agents 5-aza-2'-cytidine and zebularine. To identify methylated C-residues, we sequenced cloned DNA fragments from bisulfite-treated genomic DNA. We identified a total of 1092 genes that showed >/=2-fold altered expression in at least one cell line; 710 showed up-regulation and 382 down-regulation. Extensive sequencing of promoters from 25 genes in eight cell lines showed an association between methylation pattern and expression in 13 genes, including... (More)
- DNA methylation is an important epigenetic modification that regulates several genes crucial for tumor development. To identify epigenetically regulated genes in bladder cancer, we performed genome wide expression analyses of eight-bladder cancer cell lines treated with the demethylating agents 5-aza-2'-cytidine and zebularine. To identify methylated C-residues, we sequenced cloned DNA fragments from bisulfite-treated genomic DNA. We identified a total of 1092 genes that showed >/=2-fold altered expression in at least one cell line; 710 showed up-regulation and 382 down-regulation. Extensive sequencing of promoters from 25 genes in eight cell lines showed an association between methylation pattern and expression in 13 genes, including both CpG island and non-CpG island genes. Overall, the methylation patterns showed a patchy appearance with short segments showing high level of methylation separated by larger segments with no methylation. This pattern was not associated with MeCP2 binding sites or with evolutionarily conserved sequences. The genes UBXD2, AQP11, and TIMP1 showed particular patchy methylation patterns. We found several high-scoring and evolutionarily conserved transcription factor binding sites affected by methylated C residues. Two of the genes, FGF18 and MMP11, that were down-regulated as response to 5-aza-2'-cytidine and zebularine treatment showed methylation at specific sites in the untreated cells indicating an activating result of methylation. Apart from identifying epigenetically regulated genes, including TGFBR1, NUPR1, FGF18, TIMP1, and MMP11, that may be of importance for bladder cancer development the presented data also highlight the organization of the modified segments in methylated promoters. (c) 2008 Wiley-Liss, Inc. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1021369
- author
- Veerla, Srinivas
LU
; Panagopoulos, Ioannis
LU
; Jin, Yuesheng
LU
; Lindgren, David
LU
and Höglund, Mattias
LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Genes, Chromosomes and Cancer
- volume
- 47
- pages
- 368 - 378
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:18196590
- wos:000254478200002
- scopus:41349113351
- pmid:18196590
- ISSN
- 1045-2257
- DOI
- 10.1002/gcc.20542
- language
- English
- LU publication?
- yes
- id
- f1009430-7db2-4852-babe-e1923145d295 (old id 1021369)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18196590?dopt=Abstract
- date added to LUP
- 2016-04-04 08:44:31
- date last changed
- 2024-02-11 00:25:16
@article{f1009430-7db2-4852-babe-e1923145d295,
abstract = {{DNA methylation is an important epigenetic modification that regulates several genes crucial for tumor development. To identify epigenetically regulated genes in bladder cancer, we performed genome wide expression analyses of eight-bladder cancer cell lines treated with the demethylating agents 5-aza-2'-cytidine and zebularine. To identify methylated C-residues, we sequenced cloned DNA fragments from bisulfite-treated genomic DNA. We identified a total of 1092 genes that showed >/=2-fold altered expression in at least one cell line; 710 showed up-regulation and 382 down-regulation. Extensive sequencing of promoters from 25 genes in eight cell lines showed an association between methylation pattern and expression in 13 genes, including both CpG island and non-CpG island genes. Overall, the methylation patterns showed a patchy appearance with short segments showing high level of methylation separated by larger segments with no methylation. This pattern was not associated with MeCP2 binding sites or with evolutionarily conserved sequences. The genes UBXD2, AQP11, and TIMP1 showed particular patchy methylation patterns. We found several high-scoring and evolutionarily conserved transcription factor binding sites affected by methylated C residues. Two of the genes, FGF18 and MMP11, that were down-regulated as response to 5-aza-2'-cytidine and zebularine treatment showed methylation at specific sites in the untreated cells indicating an activating result of methylation. Apart from identifying epigenetically regulated genes, including TGFBR1, NUPR1, FGF18, TIMP1, and MMP11, that may be of importance for bladder cancer development the presented data also highlight the organization of the modified segments in methylated promoters. (c) 2008 Wiley-Liss, Inc.}},
author = {{Veerla, Srinivas and Panagopoulos, Ioannis and Jin, Yuesheng and Lindgren, David and Höglund, Mattias}},
issn = {{1045-2257}},
language = {{eng}},
pages = {{368--378}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Genes, Chromosomes and Cancer}},
title = {{Promoter analysis of epigenetically controlled genes in bladder cancer.}},
url = {{http://dx.doi.org/10.1002/gcc.20542}},
doi = {{10.1002/gcc.20542}},
volume = {{47}},
year = {{2008}},
}