Phenotypic plasticity and the epigenetics of human disease

被引:1138
作者
Feinberg, Andrew P.
机构
[1] Johns Hopkins Univ, Sch Med, Dept Med, Inst Basic Biomed Sci, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Inst Basic Biomed Sci, Baltimore, MD 21205 USA
关键词
D O I
10.1038/nature05919
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
It is becoming clear that epigenetic changes are involved in human disease as well as during normal development. A unifying theme of disease epigenetics is defects in phenotypic plasticity - cells' ability to change their behaviour in response to internal or external environmental cues. This model proposes that hereditary disorders of the epigenetic apparatus lead to developmental defects, that cancer epigenetics involves disruption of the stem-cell programme, and that common diseases with late-onset phenotypes involve interactions between the epigenome, the genome and the environment. Increased understanding of epigenetic-disease mechanisms could lead to disease-risk stratification for targeted intervention and to targeted therapies.
引用
收藏
页码:433 / 440
页数:8
相关论文
共 101 条
[31]   Epigenetic remodeling in colorectal cancer results in coordinate gene suppression across an entire chromosome band [J].
Frigola, J ;
Song, J ;
Stirzaker, C ;
Hinshelwood, RA ;
Peinado, MA ;
Clark, SJ .
NATURE GENETICS, 2006, 38 (05) :540-549
[32]   Induction of tumors in mice by genomic hypomethylation [J].
Gaudet, F ;
Hodgson, JG ;
Eden, A ;
Jackson-Grusby, L ;
Dausman, J ;
Gray, JW ;
Leonhardt, H ;
Jaenisch, R .
SCIENCE, 2003, 300 (5618) :489-492
[33]  
Gibbons RJ, 2000, AM J MED GENET, V97, P204, DOI 10.1002/1096-8628(200023)97:3<204::AID-AJMG1038>3.0.CO
[34]  
2-X
[35]   Alcohol, one-carbon metabolism, and colorectal cancer: Recent insights from molecular studies [J].
Giovannucci, E .
JOURNAL OF NUTRITION, 2004, 134 (09) :2475S-2481S
[36]   Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach [J].
Gius, D ;
Cui, HM ;
Bradbury, CM ;
Cook, J ;
Smart, DDK ;
Zhao, SP ;
Young, L ;
Brandenburg, SA ;
Hu, YL ;
Bisht, KS ;
Ho, AS ;
Mattson, D ;
Sun, LC ;
Munson, PJ ;
Chuang, EY ;
Mitchell, JB ;
Feinberg, AP .
CANCER CELL, 2004, 6 (04) :361-371
[37]   EPIGENETIC CHANGES MAY CONTRIBUTE TO THE FORMATION AND SPONTANEOUS REGRESSION OF RETINOBLASTOMA [J].
GREGER, V ;
PASSARGE, E ;
HOPPING, W ;
MESSMER, E ;
HORSTHEMKE, B .
HUMAN GENETICS, 1989, 83 (02) :155-158
[38]   Soluble IGF2 receptor rescues ApcMin/+ intestinal adenoma progression induced by Igf2 loss of imprinting [J].
Harper, J ;
Burns, JL ;
Foulstone, EJ ;
Pignatelli, M ;
Zaina, S ;
Hassan, AB .
CANCER RESEARCH, 2006, 66 (04) :1940-1948
[39]   Preference of DNA methyltransferases for CpG islands in mouse embryonic stem cells [J].
Hattori, N ;
Abe, T ;
Hattori, N ;
Suzuki, M ;
Matsuyama, T ;
Yoshida, S ;
Li, E ;
Shiota, K .
GENOME RESEARCH, 2004, 14 (09) :1733-1740
[40]   Reprogramming of a melanoma genome by nuclear transplantation [J].
Hochedlinger, K ;
Blelloch, R ;
Brennan, C ;
Yamada, Y ;
Kim, MJ ;
Chin, L ;
Jaenisch, R .
GENES & DEVELOPMENT, 2004, 18 (15) :1875-1885