Type

Journal Article

Authors

Trudee Fair
Pat Lonergan
Alan M O'Doherty
Solomon Mamo
Shirley A Ellis
Abdullah al Naib
Grace M O'Gorman

Subjects

Biochemistry

Topics
genetics mutagenesis site directed hla antigens stat6 transcription factor interferon type i endometrium interleukin 3 pharmacology dna methylation animals blastocyst hla g antigens binding sites transfection interleukin 4 histocompatibility antigens class i cell line rna messenger promoter regions genetic trophoblastin metabolism pregnancy proteins interferon gamma gene expression regulation dna chemistry pregnancy female cattle progesterone drug effects

Regulation of a bovine nonclassical major histocompatibility complex class I gene promoter. (2010)

Abstract Studies have shown in humans and other species that the major histocompatibility complex class I (MHC-I) region is involved at a number of levels in the establishment and maintenance of pregnancy. The aim of this study was to characterize how a bovine nonclassical MHC-I gene (NC1) is regulated. Initial serial deletion experiments of a 2-kb fragment of the NC1 promoter identified regions with positive regulatory elements in the proximal promoter and evidence for a silencer module(s) further upstream that cooperatively contributed to constitutive NC1 expression. The cytokines interferon tau (IFNT), interferon gamma (IFNG), and interleukin 4 (IL4) significantly increased luciferase expression in NC1 promoter reporter constructs and endogenous NC1 mRNA levels in a bovine endometrial cell line. In addition, IFNG, IL3, IL4, and progesterone significantly increased Day 7 bovine blastocyst NC1 mRNA expression when supplemented during in vitro embryo culture. Site-directed mutagenesis analysis identified a STAT6 binding site that conferred IL4 responsiveness in the NC1 proximal promoter. Furthermore, methylation treatment of the proximal promoter, which contains a CpG island, completely abrogated constitutive NC1 expression. Overall, the findings presented here suggest that constitutive NC1 expression is regulated positively by elements in the proximal promoter, which are further controlled by upstream silencer modules. The promoter is responsive to IFNT, IFNG, and IL4, suggesting possible roles for these cytokines in bovine preimplantation embryo survival and/or maternal-fetal tolerance. Our studies also suggest that methylation of the proximal promoter, in particular, could play a significant role in regulating NC1 expression.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Trudee Fair, Pat Lonergan, Alan M O'Doherty, Solomon Mamo, Shirley A Ellis, Abdullah al Naib, Grace M O'Gorman

Experts in our system

1
T Fair
University College Dublin
Total Publications: 71
 
2
Pat Lonergan
University College Dublin
Total Publications: 26
 
3
Alan M O'Doherty
University College Dublin
Total Publications: 18