Developmental programming of CpG island methylation profiles in the human genome

Ravid Straussman, Deborah Nejman, Douglas Roberts, Israel Steinfeld, Barak Blum, Nissim Benvenisty, Itamar Simon, Zohar Yakhini, Howard Cedar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

320 Scopus citations


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.

Original languageAmerican English
Pages (from-to)564-571
Number of pages8
JournalNature Structural and Molecular Biology
Issue number5
StatePublished - May 2009

Bibliographical note

Funding Information:
This work was supported by the Israel Cancer Research Fund (H.C.), the Rosetrees Trust (H.C.), Lewis Sanders (H.C.), both Philip Morris USA Inc. and Philip Morris International (R.S.) and an Agilent University Relations grant (H.C.).


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