Developmental programming of CpG island methylation profiles in the human genome.
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.
Department of Cellular Biochemistry and Human Genetics, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ravid
R
Straussman
Deborah
D
Nejman
Douglas
D
Roberts
Israel
I
Steinfeld
Barak
B
Blum
Nissim
N
Benvenisty
Itamar
I
Simon
Zohar
Z
Yakhini
Howard
H
Cedar
D000465:Algorithms; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D047108:Embryonic Development / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D024363:Transcription Initiation Site