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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-3-1
pubmed:abstractText
Expression of ovine interferon-tau (oIFNtau) genes, essential for the maternal recognition of pregnancy in ruminant ungulates, is restricted to the trophoblast and is not detected in any other cell types or tissues. Substantial secretion of oIFNtau starts on day 12-13 of pregnancy (day 0 = day of estrus), reaches the highest on day 16-17, and then declines rapidly. Ovine IFNtau mRNA, on the other hand, reaches the highest level on day 14 of pregnancy, 2-3 days before peak production of the protein. In this study, day 14 and 17 conceptuses treated with 5-aza-2'-deoxycytidine, an inhibitor of DNA methylation, were cultured in vitro and only day 17, not day 14, conceptuses resulted in upregulation of oIFNtau gene expression. To gain insight into the molecular mechanism of oIFNtau gene downregulation, the methylation status within 1 kb of the 5'-flanking region of oIFNtau-o10 gene was investigated: CpG dinucleotides of this gene in day 14 ovine conceptuses were hypomethylated compared to day 20 conceptuses or other tissues. In vitro methylation of oIFNtau-o10-reporter constructs caused suppression of reporter activity in transient transfections. Cotransfection of methyl-CpG-binding protein (MeCP2) with the reporter construct elicited further suppression of the reporter activity. In electrophoretic mobility shift assay (EMSA), patterns of shifted bands did not show much difference between methylated and unmethylated probes in distal regions, but exhibited differences in the proximal region of upstream sequences of the oIFNtau gene. These results provide evidence that changes in the degree of DNA methylation could be one of the major mechanisms leading to downregulation of the oIFNtau-o10 gene during early gestation, and possibly its silencing in nonconceptus tissues.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1040-452X
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
396-405
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14991730-Animals, pubmed-meshheading:14991730-Cell Line, pubmed-meshheading:14991730-DNA Methylation, pubmed-meshheading:14991730-Down-Regulation, pubmed-meshheading:14991730-Embryo, Mammalian, pubmed-meshheading:14991730-Embryo, Nonmammalian, pubmed-meshheading:14991730-Enzyme Inhibitors, pubmed-meshheading:14991730-Female, pubmed-meshheading:14991730-Gene Expression Regulation, Developmental, pubmed-meshheading:14991730-Hydroxamic Acids, pubmed-meshheading:14991730-Interferon Type I, pubmed-meshheading:14991730-Pregnancy, pubmed-meshheading:14991730-Pregnancy Proteins, pubmed-meshheading:14991730-Promoter Regions, Genetic, pubmed-meshheading:14991730-Ships, pubmed-meshheading:14991730-Transcription Factors, pubmed-meshheading:14991730-Transcriptional Activation, pubmed-meshheading:14991730-Uterus
pubmed:year
2004
pubmed:articleTitle
Increase in DNA methylation downregulates conceptus interferon-tau gene expression.
pubmed:affiliation
Laboratory of Animal Breeding, Faculty of Agriculture, The University of Tokyo, Tokyo, Japan.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't