Developmental Programming of CpG Island Methylation Profiles in the Human Genome

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2009 Apr 21

PMID 19377480

Citations 192

Authors

Ravid Straussman

Deborah Nejman

Douglas Roberts

Israel Steinfeld

Barak Blum

Nissim Benvenisty

Itamar Simon

Zohar Yakhini

Howard Cedar

Affiliations

Soon will be listed here.

Abstract

CpG island-like sequences are commonly thought to provide the sole signals for designating constitutively unmethylated regions in the genome, thus generating open chromatin domains within a sea of global repression. Using a new database obtained from comprehensive microarray analysis, we show that unmethylated regions (UMRs) seem to be formed during early embryogenesis, not as a result of CpG-ness, but rather through the recognition of specific sequence motifs closely associated with transcription start sites. This same system probably brings about the resetting of pluripotency genes during somatic cell reprogramming. The data also reveal a new class of nonpromoter UMRs that become de novo methylated in a tissue-specific manner during development, and this process may be involved in gene regulation. In short, we show that UMRs are an important aspect of genome structure that have a dynamic role in development.

Citing Articles

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References

Rauch T, Wu X, Zhong X, Riggs A, Pfeifer G . A human B cell methylome at 100-base pair resolution. Proc Natl Acad Sci U S A. 2009; 106(3):671-8. PMC: 2621253. DOI: 10.1073/pnas.0812399106. View

Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W . Epigenetic reprogramming in mouse primordial germ cells. Mech Dev. 2002; 117(1-2):15-23. DOI: 10.1016/s0925-4773(02)00181-8. View

Guenther M, Levine S, Boyer L, Jaenisch R, Young R . A chromatin landmark and transcription initiation at most promoters in human cells. Cell. 2007; 130(1):77-88. PMC: 3200295. DOI: 10.1016/j.cell.2007.05.042. View

Zhao X, Han X, Chew J, Liu J, Chiu K, Choo A . Whole-genome mapping of histone H3 Lys4 and 27 trimethylations reveals distinct genomic compartments in human embryonic stem cells. Cell Stem Cell. 2008; 1(3):286-98. DOI: 10.1016/j.stem.2007.08.004. View

Ma D, Chiang C, Ponnusamy K, Ming G, Song H . G9a and Jhdm2a regulate embryonic stem cell fusion-induced reprogramming of adult neural stem cells. Stem Cells. 2008; 26(8):2131-41. PMC: 4059405. DOI: 10.1634/stemcells.2008-0388. View

Illingworth R, Kerr A, DeSousa D, Jorgensen H, Ellis P, Stalker J . A novel CpG island set identifies tissue-specific methylation at developmental gene loci. PLoS Biol. 2008; 6(1):e22. PMC: 2214817. DOI: 10.1371/journal.pbio.0060022. View

Farthing C, Ficz G, Ng R, Chan C, Andrews S, Dean W . Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogramming of pluripotency genes. PLoS Genet. 2008; 4(6):e1000116. PMC: 2432031. DOI: 10.1371/journal.pgen.1000116. View

Antequera F, Boyes J, Bird A . High levels of de novo methylation and altered chromatin structure at CpG islands in cell lines. Cell. 1990; 62(3):503-14. DOI: 10.1016/0092-8674(90)90015-7. View

He Y, Vogelstein B, Velculescu V, Papadopoulos N, Kinzler K . The antisense transcriptomes of human cells. Science. 2008; 322(5909):1855-7. PMC: 2824178. DOI: 10.1126/science.1163853. View

10.

Reynaud C, Bruno C, Boullanger P, Grange J, Barbesti S, Niveleau A . Monitoring of urinary excretion of modified nucleosides in cancer patients using a set of six monoclonal antibodies. Cancer Lett. 1992; 61(3):255-62. DOI: 10.1016/0304-3835(92)90296-8. View

11.

Cowan C, Atienza J, Melton D, Eggan K . Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science. 2005; 309(5739):1369-73. DOI: 10.1126/science.1116447. View

12.

Yu W, Gius D, Onyango P, Muldoon-Jacobs K, Karp J, Feinberg A . Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature. 2008; 451(7175):202-6. PMC: 2743558. DOI: 10.1038/nature06468. View

13.

Koslowski M, Bell C, Seitz G, Lehr H, Roemer K, Muntefering H . Frequent nonrandom activation of germ-line genes in human cancer. Cancer Res. 2004; 64(17):5988-93. DOI: 10.1158/0008-5472.CAN-04-1187. View

14.

Siegfried Z, Eden S, Mendelsohn M, Feng X, Tsuberi B, Cedar H . DNA methylation represses transcription in vivo. Nat Genet. 1999; 22(2):203-6. DOI: 10.1038/9727. View

15.

Simpson A, Caballero O, Jungbluth A, Chen Y, Old L . Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer. 2005; 5(8):615-25. DOI: 10.1038/nrc1669. View

16.

Brandeis M, Frank D, Keshet I, Siegfried Z, Mendelsohn M, Nemes A . Sp1 elements protect a CpG island from de novo methylation. Nature. 1994; 371(6496):435-8. DOI: 10.1038/371435a0. View

17.

Lorincz M, Schubeler D . RNA polymerase II: just stopping by. Cell. 2007; 130(1):16-8. DOI: 10.1016/j.cell.2007.06.040. View

18.

Monk M, Boubelik M, Lehnert S . Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development. 1987; 99(3):371-82. DOI: 10.1242/dev.99.3.371. View

19.

Keshet I, Schlesinger Y, Farkash S, Rand E, Hecht M, Segal E . Evidence for an instructive mechanism of de novo methylation in cancer cells. Nat Genet. 2006; 38(2):149-53. DOI: 10.1038/ng1719. View

20.

MacLeod D, Charlton J, Mullins J, Bird A . Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes Dev. 1994; 8(19):2282-92. DOI: 10.1101/gad.8.19.2282. View