Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1995-11-27
pubmed:abstractText
Estrogen therapy has been reported to cause multiple alterations in hemostasis and to increase blood levels of several procoagulants, including Hageman factor [factor XII (FXII)]. Liver FXII gene expression has been investigated in ovariectomized rats, treated or not with 17 beta-estradiol. A 6-fold stimulation of FXII gene transcription was observed in treated compared to untreated animals, indicating that 17 beta-estradiol is able to induce FXII gene expression in vivo. We have recently shown that human FXII promoter contains an imperfect palindrome, 5'-GGGCAnnnTGACC-3', at position -43/-31 resembling the consensus estrogen-responsive element (ERE). Portions of different length of the FXII promoter were fused to the chloramphenicol acetyltransferase (CAT) coding sequence and transiently cotransfected with human estrogen receptor (ER) into NIH3T3 and HepG2 cells in the presence or absence of 17 beta-estradiol. A 230-base pair fragment of FXII promoter, spanning nucleotides - 181/49, conferred a strong estrogen responsiveness to the CAT reporter gene, suggesting that a functional ERE resides in this region. Cognate receptors, such as those for thyroid hormone or retinoic acid, did not stimulate CAT activity. Gel mobility assays demonstrated a specific interaction between ER and the 230-bp FXII promoter fragment containing the putative ERE palindrome. Similar results were obtained when an oligonucleotide spanning the consensus ERE was used; the complex between ER and FXII promoter sequences was supershifted after the addition of an anti-ER monoclonal antibody. Insertion of FXII-ERE into the heterologous thymidine kinase promoter conferred a strong estrogen responsiveness that was abolished by mutations of the 5'-half of the palindrome. These results represent the first demonstration at the molecular level of the regulation of a blood coagulation factor gene by 17 beta-estradiol as well as the first identification of a functional ERE within this class of genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
136
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5076-83
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:7588244-Animals, pubmed-meshheading:7588244-Base Sequence, pubmed-meshheading:7588244-Chloramphenicol O-Acetyltransferase, pubmed-meshheading:7588244-Estradiol, pubmed-meshheading:7588244-Factor XII, pubmed-meshheading:7588244-Female, pubmed-meshheading:7588244-Gene Expression Regulation, pubmed-meshheading:7588244-Humans, pubmed-meshheading:7588244-Liver, pubmed-meshheading:7588244-Molecular Sequence Data, pubmed-meshheading:7588244-Ovariectomy, pubmed-meshheading:7588244-Promoter Regions, Genetic, pubmed-meshheading:7588244-RNA, Messenger, pubmed-meshheading:7588244-Rats, pubmed-meshheading:7588244-Rats, Sprague-Dawley, pubmed-meshheading:7588244-Receptors, Estrogen, pubmed-meshheading:7588244-Recombinant Fusion Proteins, pubmed-meshheading:7588244-Repetitive Sequences, Nucleic Acid, pubmed-meshheading:7588244-Transfection
pubmed:year
1995
pubmed:articleTitle
Molecular basis of estrogen regulation of Hageman factor XII gene expression.
pubmed:affiliation
Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Rome, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't