Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1998-12-21
pubmed:abstractText
Before they can deliver their effector functions, CD4+ Th cells must differentiate into Th1 or Th2 subsets. We have prepared reporter transgenic mice that express the luciferase gene under the control of proximal (prox.IFN-gamma) and distal (dist.IFN-gamma) regulatory elements from the IFN-gamma promoter to permit investigation of mechanisms that regulate IFN-gamma gene transcription during Th cell differentiation. Precursor Th cells (pTh) contain high levels of cAMP response element binding protein-activation transcription factor-1 (CREB-ATF1) proteins that bind these promoter elements from the IFN-gamma gene, and these cells fail to express promoter activity. Restimulated effector Th (eTh) cells have reduced levels of CREB-ATF1 proteins, their nuclear extracts exhibit reduced CREB-ATF1 binding and greater Jun and Jun-ATF2 binding to dist.IFN-gamma), and eTh cells express promoter activity. CREB directly competes with effector T cell nuclear proteins for dist.IFN-gamma binding, and overexpression of CREB inhibits both prox.IFN-gamma- and dist.IFN-gamma-directed transcription in Jurkat T cells. IL-12-stimulated Thl differentiation increases dist.IFN-gamma activity in restimulated eTh1 cells; eTh1 nuclear extracts form increased levels of Jun-ATF2-dist.IFN-gamma complexes. Taken together, these data suggest that both de-repression and trans-activation contribute to the induction of IFN-gamma gene transcription during Th1 differentiation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
161
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6105-12
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9834094-Animals, pubmed-meshheading:9834094-Binding, Competitive, pubmed-meshheading:9834094-Cell Differentiation, pubmed-meshheading:9834094-Cells, Cultured, pubmed-meshheading:9834094-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:9834094-Down-Regulation, pubmed-meshheading:9834094-Interferon-gamma, pubmed-meshheading:9834094-Interleukin-12, pubmed-meshheading:9834094-Mice, pubmed-meshheading:9834094-Mice, Inbred C57BL, pubmed-meshheading:9834094-Mice, Inbred CBA, pubmed-meshheading:9834094-Mice, Transgenic, pubmed-meshheading:9834094-Nuclear Proteins, pubmed-meshheading:9834094-Promoter Regions, Genetic, pubmed-meshheading:9834094-Protein Binding, pubmed-meshheading:9834094-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:9834094-T-Lymphocytes, Helper-Inducer, pubmed-meshheading:9834094-Th1 Cells, pubmed-meshheading:9834094-Transcription Factor AP-1
pubmed:year
1998
pubmed:articleTitle
Regulation of the activity of IFN-gamma promoter elements during Th cell differentiation.
pubmed:affiliation
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't