Sp1 elements protect a CpG island from de novo methylation.
Animal somatic cell DNA is characterized by a bimodal pattern of methylation: tissue-specific genes are methylated in most cell types whereas housekeeping genes have 5' CpG islands which are constitutively unmethylated. Because methyl moieties derived from the gametes are erased in the morula and early blastula, this profile must be re-established in every generation; this is apparently accomplished by a wave of non-CpG island de novo methylation that occurs at implantation. Using transfection into embryonic stem cells and transgenic mice as a model system, we now show that Sp1 elements play a key role in protecting a CpG island in the adenine phosphoribosyltransferase (APRT) gene from de novo methylation. This recognition mechanism represents a critical step in embryogenesis, as it is responsible for setting up the correct genome methylation pattern which, in turn, is involved in regulating basal gene expression in the organism.
Brandeis
M
M
Department of Cellular Biochemistry, Hebrew University Medical School, Jerusalem, Israel.
Frank
D
D
Keshet
I
I
Siegfried
Z
Z
Mendelsohn
M
M
Nemes
A
A
Temper
V
V
Razin
A
A
Cedar
H
H
D000228:Adenine Phosphoribosyltransferase / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D008745:Methylation; D008969:Molecular Sequence Data; D012045:Regulatory Sequences, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013234:Stem Cells
D000228:Adenine Phosphoribosyltransferase; D004247:DNA; D015226:Dinucleoside Phosphates; D016329:Sp1 Transcription Factor; C015772:CpG dinucleotide