Resource abstract

Nature Structural & Molecular Biology 16, 564 - 571 (2009)
Published online: 19 April 2009 | doi:10.1038/nsmb.1594

Developmental programming of CpG island methylation profiles in the human genome

Ravid Straussman1,7, Deborah Nejman1, Douglas Roberts2, Israel Steinfeld3, Barak Blum4, Nissim Benvenisty4, Itamar Simon5, Zohar Yakhini3,6 & Howard Cedar1

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.

  1. Department of Cellular Biochemistry and Human Genetics, The Hebrew University–Hadassah Medical School, Jerusalem, Israel.
  2. Agilent Technologies Inc., Santa Clara, California, USA.
  3. Agilent Laboratories, Tel Aviv, Israel.
  4. Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.
  5. Department of Molecular Biology, The Hebrew University–Hadassah Medical School, Jerusalem, Israel.
  6. Department of Computer Sciences, Technion–Israel Institute of Technology, Haifa, Israel.
  7. Present address: The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

Correspondence to: Howard Cedar1 e-mail:


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