TY - JOUR
T1 - Developmental programming of CpG island methylation profiles in the human genome
AU - Straussman, Ravid
AU - Nejman, Deborah
AU - Roberts, Douglas
AU - Steinfeld, Israel
AU - Blum, Barak
AU - Benvenisty, Nissim
AU - Simon, Itamar
AU - Yakhini, Zohar
AU - Cedar, Howard
N1 - 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.).
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=66149147557&partnerID=8YFLogxK
U2 - 10.1038/nsmb.1594
DO - 10.1038/nsmb.1594
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C2 - 19377480
AN - SCOPUS:66149147557
SN - 1545-9993
VL - 16
SP - 564
EP - 571
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 5
ER -