Inflammation-associated DNA methylation patterns in epithelium of ulcerative colitis

被引:40
作者
Barnicle, Alan [1 ,2 ]
Seoighe, Cathal [2 ]
Greally, John M. [3 ,4 ]
Golden, Aaron [2 ,3 ,4 ,5 ]
Egan, Laurence J. [1 ]
机构
[1] Natl Univ Ireland, Sch Med, Clin Pharmacol, Galway, Ireland
[2] Natl Univ Ireland, Sch Math Stat & Appl Math, Galway, Ireland
[3] Albert Einstein Coll Med, Ctr Epigenom, Morris Pk Ave, Bronx, NY 10467 USA
[4] Albert Einstein Coll Med, Dept Genet, Div Computat Genet, Morris Pk Ave, Bronx, NY 10467 USA
[5] Yeshiva Univ, Dept Math Sci, 2495 Amsterdam Ave, New York, NY 10033 USA
关键词
DNA methylation; intestinal epithelial cell; inflammatory bowel disease; transcriptome; ulcerative colitis; INTESTINAL EPITHELIUM; GENE-EXPRESSION; CHROMATIN-STATE; BOWEL-DISEASE; CELLS; GROWTH; TRANSCRIPTION; MICROBIOTA; MUCOSA; CLASSIFICATION;
D O I
10.1080/15592294.2017.1334023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Aberrant DNA methylation patterns have been reported in inflamed tissues and may play a role in disease. We studied DNA methylation and gene expression profiles of purified intestinal epithelial cells from ulcerative colitis patients, comparing inflamed and non-inflamed areas of the colon. We identified 577 differentially methylated sites (false discovery rate <0.2) mapping to 210 genes. From gene expression data from the same epithelial cells, we identified 62 differentially expressed genes with increased expression in the presence of inflammation at prostate cancer susceptibility genes PRAC1 and PRAC2. Four genes showed inverse correlation between methylation and gene expression; ROR1, GXYLT2, FOXA2, and, notably, RARB, a gene previously identified as a tumor suppressor in colorectal adenocarcinoma as well as breast, lung and prostate cancer. We highlight targeted and specific patterns of DNA methylation and gene expression in epithelial cells from inflamed colon, while challenging the importance of epithelial cells in the pathogenesis of chronic inflammation.
引用
收藏
页码:591 / 606
页数:16
相关论文
共 77 条
[1]   An atlas of active enhancers across human cell types and tissues [J].
Andersson, Robin ;
Gebhard, Claudia ;
Miguel-Escalada, Irene ;
Hoof, Ilka ;
Bornholdt, Jette ;
Boyd, Mette ;
Chen, Yun ;
Zhao, Xiaobei ;
Schmidl, Christian ;
Suzuki, Takahiro ;
Ntini, Evgenia ;
Arner, Erik ;
Valen, Eivind ;
Li, Kang ;
Schwarzfischer, Lucia ;
Glatz, Dagmar ;
Raithel, Johanna ;
Lilje, Berit ;
Rapin, Nicolas ;
Bagger, Frederik Otzen ;
Jorgensen, Mette ;
Andersen, Peter Refsing ;
Bertin, Nicolas ;
Rackham, Owen ;
Burroughs, A. Maxwell ;
Baillie, J. Kenneth ;
Ishizu, Yuri ;
Shimizu, Yuri ;
Furuhata, Erina ;
Maeda, Shiori ;
Negishi, Yutaka ;
Mungall, Christopher J. ;
Meehan, Terrence F. ;
Lassmann, Timo ;
Itoh, Masayoshi ;
Kawaji, Hideya ;
Kondo, Naoto ;
Kawai, Jun ;
Lennartsson, Andreas ;
Daub, Carsten O. ;
Heutink, Peter ;
Hume, David A. ;
Jensen, Torben Heick ;
Suzuki, Harukazu ;
Hayashizaki, Yoshihide ;
Mueller, Ferenc ;
Forrest, Alistair R. R. ;
Carninci, Piero ;
Rehli, Michael ;
Sandelin, Albin .
NATURE, 2014, 507 (7493) :455-+
[2]  
[Anonymous], CANC BIOL THER
[3]   MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis [J].
Araki, A ;
Kanai, T ;
Ishikura, T ;
Makita, S ;
Uraushihara, K ;
Iiyama, R ;
Totsuka, T ;
Takeda, K ;
Akira, S ;
Watanabe, M .
JOURNAL OF GASTROENTEROLOGY, 2005, 40 (01) :16-23
[4]   REGULATION OF INTESTINAL EPITHELIAL-CELL GROWTH BY TRANSFORMING GROWTH-FACTOR TYPE-BETA [J].
BARNARD, JA ;
BEAUCHAMP, RD ;
COFFEY, RJ ;
MOSES, HL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (05) :1578-1582
[5]   Differential DNA methylation patterns of homeobox genes in proximal and distal colon epithelial cells [J].
Barnicle, Alan ;
Seoighe, Cathal ;
Golden, Aaron ;
Greally, John M. ;
Egan, Laurence J. .
PHYSIOLOGICAL GENOMICS, 2016, 48 (04) :257-273
[6]   DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines [J].
Bell, Jordana T. ;
Pai, Athma A. ;
Pickrell, Joseph K. ;
Gaffney, Daniel J. ;
Pique-Regi, Roger ;
Degner, Jacob F. ;
Gilad, Yoav ;
Pritchard, Jonathan K. .
GENOME BIOLOGY, 2011, 12 (01)
[7]   DNA methylation patterns and epigenetic memory [J].
Bird, A .
GENES & DEVELOPMENT, 2002, 16 (01) :6-21
[8]   Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes [J].
Blattler, Adam ;
Yao, Lijing ;
Witt, Heather ;
Guo, Yu ;
Nicolet, Charles M. ;
Berman, Benjamin P. ;
Farnham, Peggy J. .
GENOME BIOLOGY, 2014, 15 (09) :469
[9]   Inter-individual variation of DNA methylation and its implications for large-scale epigenome mapping [J].
Bock, Christoph ;
Walter, Joern ;
Paulsen, Martina ;
Lengauer, Thomas .
NUCLEIC ACIDS RESEARCH, 2008, 36 (10)
[10]   A comparison of normalization methods for high density oligonucleotide array data based on variance and bias [J].
Bolstad, BM ;
Irizarry, RA ;
Åstrand, M ;
Speed, TP .
BIOINFORMATICS, 2003, 19 (02) :185-193