Association of tissue-specific differentially methylated regions (TDMs) with differential gene expression.
Early studies proposed that DNA methylation could have a role in regulating gene expression during development [Riggs, A.D. (1975) Cytogenet. Cell Genet. 14, 9-25]. However, some studies of DNA methylation in known tissue-specific genes during development do not support a major role for DNA methylation. In the results presented here, tissue-specific differentially methylated regions (TDMs) were first identified, and then expression of genes associated with these regions correlated with methylation status. Restriction landmark genomic scanning (RLGS) was used in conjunction with virtual RLGS to identify 150 TDMs [Matsuyama, T., Kimura, M.T., Koike, K., Abe, T., Nakao, T., Asami, T., Ebisuzaki, T., Held, W.A., Yoshida, S. & Nagase, H. (2003) Nucleic Acids Res. 31, 4490-4496]. Analysis of 14 TDMs by methylation-specific PCR and by bisulfite genomic sequencing confirms that the regions identified by RLGS are differentially methylated in a tissue-specific manner. The results indicate that 5% or more of the CpG islands are TDMs, disputing the general notion that all CpG islands are unmethylated. Some of the TDMs are within 5' promoter CpG islands of genes, which exhibit a tissue-specific expression pattern that is consistent with methylation status and a role in tissue differentiation.
Song
Fei
F
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Smith
Joseph F
JF
Kimura
Makoto T
MT
Morrow
Arlene D
AD
Matsuyama
Tomoki
T
Nagase
Hiroki
H
Held
William A
WA
D000818:Animals; D018899:CpG Islands; D019175:DNA Methylation; D015870:Gene Expression; D016678:Genome; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
Cell. 1999 Nov 24;99(5):451-4
10589672
Nat Rev Genet. 2004 Jun;5(6):446-55
15153997
Genes Dev. 2000 Apr 1;14(7):841-53
10766740
Dev Cell. 2001 Dec;1(6):749-58
11740937
Cytogenet Genome Res. 2004;105(2-4):325-34
15237220
Genome Res. 2004 Sep;14(9):1733-40
15310660
Science. 1975 Jan 24;187(4173):226-32
1111098
Cytogenet Cell Genet. 1975;14(1):9-25
1093816
Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9523-7
1946366
Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1827-31
1542678
Mamm Genome. 1991;1(2):78-83
1799791
Electrophoresis. 1993 Apr;14(4):251-8
8388788
Biotechniques. 1993 Sep;15(3):532-4, 536-7
7692896
Electrophoresis. 1995 Feb;16(2):218-26
7774562
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9821-6
8790415
Mol Cell Biol. 1999 Jan;19(1):164-72
9858541
Genes Dev. 1999 Jan 1;13(1):26-34
9887097
Cell. 1999 Jan 22;96(2):185-93
9988214
Mol Cell Biol. 1999 Nov;19(11):7327-35
10523621
Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4465-70
11904358
Genome Res. 2002 Apr;12(4):543-54
11932239
Nat Genet. 2002 Jun;31(2):175-9
12021783
Nat Rev Genet. 2002 Sep;3(9):662-73
12209141
Genes Cells. 2002 Sep;7(9):961-9
12296826
Bioinformatics. 2002 Nov;18(11):1427-31
12424112
Nature. 2002 Dec 5;420(6915):520-62
12466850
Nucleic Acids Res. 2003 Aug 1;31(15):4490-6
12888509
N Engl J Med. 2003 Nov 20;349(21):2042-54
14627790
Nat Genet. 2000 Feb;24(2):132-8
10655057