Developmental alteration of the chromatin state at promoter/replication origin region of the aldolase B locus precedes transcriptional activation in the liver.
Liver-specific expression of the rat aldolase B (AldB) gene is conferred by proximal promoter region (-200 bp to + 1 bp), which is centered on an origin region of DNA replication. Transcriptional activation of the gene in the liver occurs during the late one-third of fetal stage. To know the mechanism involved in such activation, we studied developmental changes in chromatin structure and in the extent of CpG methylation in the promoter/origin region of the gene. At an early fetal stage, when the AldB gene in the liver is not yet activated, the gene chromatin had two DNase 1-hypersensitive sites in the promoter region. One corresponded to that typical of AldB-expressing cells in the adult. The other, located approximately 200 bp upstream of the above site, disappeared as the activation of transcription started. A CpG dinucleotide in the promoter/origin region was heavily methylated at an early stage of gestation, but progressively demethylated as the liver develops. This CpG site is located at the center of an important binding site for a transcription factor. These changes occurred early in the fetal stage, prior to the gene activation, and were thus thought to be associated with differentiation of the liver cell or with cessation of cell proliferation.
Ito
K
K
Institute for Cell Biology and Genetics, Faculty of Agriculture, Iwate University, Japan.
Tsutsumi
R
R
Ishikawa
K
K
Tsutsumi
K
K
D000818:Animals; D001483:Base Sequence; D002843:Chromatin; D018076:DNA, Complementary; D015226:Dinucleoside Phosphates / Q000378:metabolism; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D018741:Replication Origin; D015533:Transcriptional Activation
D002843:Chromatin; D018076:DNA, Complementary; D015226:Dinucleoside Phosphates; D005634:Fructose-Bisphosphate Aldolase; C015772:CpG dinucleotide