Published online before print
March 20, 2002, 10.1101/gr.224102. Article published online before print in March 2002
Vol. 12, Issue 4, 543-554, April 2002
A Genome-Wide Screen for Normally Methylated Human CpG Islands That Can Identify Novel Imprinted Genes
Liora Z.
Strichman-Almashanu,1,4,5
Richard S.
Lee,1,5
Patrick O.
Onyango,1
Elizabeth
Perlman,2
Folke
Flam,3
Matthew B.
Frieman,1 and
Andrew P.
Feinberg1,6
1 Institute of Genetic Medicine and Departments of
Medicine, Oncology, Molecular Biology and Genetics, and
2 Pathology, Johns Hopkins University School of Medicine,
Baltimore, Maryland 21205, USA; 3 Karolinska Institute,
Stockholm, Sweden
DNA methylation is a covalent modification of the nucleotide
cytosine that is stably inherited at the dinucleotide CpG by somatic
cells, and 70% of CpG dinucleotides in the genome are methylated. The
exception to this pattern of methylation are CpG islands, CpG-rich
sequences that are protected from methylation, and generally are
thought to be methylated only on the inactive X-chromosome and in
tumors, as well as differentially methylated regions (DMRs) in the
vicinity of imprinted genes. To identify chromosomal regions that might
harbor imprinted genes, we devised a strategy for isolating a library
of normally methylated CpG islands. Most of the methylated CpG islands
represented high copy number dispersed repeats. However, 62 unique
clones in the library were characterized, all of which were methylated
and GC-rich, with a GC content >50%. Of these, 43 clones also showed
a CpGobs/CpGexp >0.6, of which 30 were studied in
detail. These unique methylated CpG islands mapped to 23 chromosomal
regions, and 12 were differentially methylated regions in uniparental
tissues of germline origin, i.e., hydatidiform moles (paternal origin)
and complete ovarian teratomas (maternal origin), even though many
apparently were methylated in somatic tissues. We term these sequences
gDMRs, for germline differentially methylated regions. At least two
gDMRs mapped near imprinted genes, HYMA1 and a novel homolog
of Elongin A and Elongin A2, which we term
Elongin A3. Surprisingly, 18 of the methylated CpG islands
were methylated in germline tissues of both parental origins,
representing a previously uncharacterized class of normally methylated
CpG islands in the genome, and which we term similarly methylated
regions (SMRs). These SMRs, in contrast to the gDMRs, were
significantly associated with telomeric band locations
(P = .0008), suggesting a potential role for SMRs in chromosome organization. At least 10 of the methylated CpG islands were
on average 85% conserved between mouse and human. These sequences will
provide a valuable resource in the search for novel imprinted genes,
for defining the molecular substrates of the normal methylome, and for
identifying novel targets for mammalian chromatin formation.
[The sequence data described in this paper have
been submitted to the GenBank data library under accession nos.
AF484557-AF484583.]
4
Present address: Center for Biotechnology Information,
National Institutes of Health, Bethesda, MD 20894, USA.
5
These authors contributed equally to this work.
6
Corresponding author.
12:543-554 ©2002 by Cold Spring Harbor Laboratory Press ISSN 1088-9051/02 $5.00
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Williams, N. Harker, E. Ktistaki, H. Veiga-Fernandes, K. Roderick, M. Tolaini, T. Norton, K. Williams, and D. Kioussis
Position effect variegation and imprinting of transgenes in lymphocytes
Nucleic Acids Res.,
April 1, 2008;
36(7):
2320 - 2329.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. P. Luedi, F. S. Dietrich, J. R. Weidman, J. M. Bosko, R. L. Jirtle, and A. J. Hartemink
Computational and experimental identification of novel human imprinted genes
Genome Res.,
December 1, 2007;
17(12):
1723 - 1730.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Suzuki, S. Sato, Y. Arai, T. Shinohara, S. Tanaka, J. M. Greally, N. Hattori, and K. Shiota
A new class of tissue-specifically methylated regions involving entire CpG islands in the mouse.
Genes Cells,
December 1, 2007;
12(12):
1305 - 1314.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Callinan and A. P. Feinberg
The emerging science of epigenomics.
Hum. Mol. Genet.,
April 15, 2006;
15(suppl_1):
R95 - R101.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Meissner, A. Gnirke, G. W. Bell, B. Ramsahoye, E. S. Lander, and R. Jaenisch
Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis
Nucleic Acids Res.,
October 13, 2005;
33(18):
5868 - 5877.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Sandovici, S. Kassovska-Bratinova, J. C. Loredo-Osti, M. Leppert, A. Suarez, R. Stewart, F. D. Bautista, M. Schiraldi, and C. Sapienza
Interindividual variability and parent of origin DNA methylation differences at specific human Alu elements
Hum. Mol. Genet.,
August 1, 2005;
14(15):
2135 - 2143.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. P. Luedi, A. J. Hartemink, and R. L. Jirtle
Genome-wide prediction of imprinted murine genes
Genome Res.,
June 1, 2005;
15(6):
875 - 884.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Song, J. F. Smith, M. T. Kimura, A. D. Morrow, T. Matsuyama, H. Nagase, and W. A. Held
Association of tissue-specific differentially methylated regions (TDMs) with differential gene expression
PNAS,
March 1, 2005;
102(9):
3336 - 3341.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Hattori, T. Abe, N. Hattori, M. Suzuki, T. Matsuyama, S. Yoshida, E. Li, and K. Shiota
Preference of DNA Methyltransferases for CpG Islands in Mouse Embryonic Stem Cells
Genome Res.,
September 1, 2004;
14(9):
1733 - 1740.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. B.M. Oudejans, J. Mulders, A. M.A. Lachmeijer, M. van Dijk, A. A.M. Konst, B. A. Westerman, I. J. van Wijk, P. A.J. Leegwater, H. D. Kato, T. Matsuda, et al.
The parent-of-origin effect of 10q22 in pre-eclamptic females coincides with two regions clustered for genes with down-regulated expression in androgenetic placentas
Mol. Hum. Reprod.,
August 1, 2004;
10(8):
589 - 598.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yamada, H. Watanabe, F. Miura, H. Soejima, M. Uchiyama, T. Iwasaka, T. Mukai, Y. Sakaki, and T. Ito
A Comprehensive Analysis of Allelic Methylation Status of CpG Islands on Human Chromosome 21q
Genome Res.,
February 1, 2004;
14(2):
247 - 266.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Paulsson, I. Panagopoulos, S. Knuutila, K. J. Jee, S. Garwicz, T. Fioretos, F. Mitelman, and B. Johansson
Formation of trisomies and their parental origin in hyperdiploid childhood acute lymphoblastic leukemia
Blood,
October 15, 2003;
102(8):
3010 - 3015.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ushijima, N. Watanabe, E. Okochi, A. Kaneda, T. Sugimura, and K. Miyamoto
Fidelity of the Methylation Pattern and Its Variation in the Genome
Genome Res.,
May 1, 2003;
13(5):
868 - 874.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. LEE
Genome-Wide Analysis of Epigenetics in Cancer
Ann. N.Y. Acad. Sci.,
March 1, 2003;
983(1):
101 - 109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Gupta, A. K. Godwin, L. Vanderveer, A. Lu, and J. Liu
Hypomethylation of the Synuclein{gamma} Gene CpG Island Promotes Its Aberrant Expression in Breast Carcinoma and Ovarian Carcinoma
Cancer Res.,
February 1, 2003;
63(3):
664 - 673.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Cui, P. Onyango, S. Brandenburg, Y. Wu, C.-L. Hsieh, and A. P. Feinberg
Loss of Imprinting in Colorectal Cancer Linked to Hypomethylation of H19 and IGF2
Cancer Res.,
November 15, 2002;
62(22):
6442 - 6446.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
