Document 0820
 DOCN  M9470820
 TI    Multiple prolactin-responsive elements mediate G1 and S phase expression
       of the interferon regulatory factor-1 gene.
 DT    9409
 AU    Stevens AM; Yu-Lee LY; Department of Microbiology and Immunology, Baylor
       College of; Medicine, Houston, Texas 77030.
 SO    Mol Endocrinol. 1994 Mar;8(3):345-55. Unique Identifier : AIDSLINE
       GENBANK/X72020
 AB    The interferon regulatory factor-1 (IRF-1) gene is both an
       immediate-early G1 phase gene and an S phase gene inducible by PRL in
       rat Nb2 T lymphocytes. To understand the mechanism by which PRL
       regulates the biphasic expression of IRF-1, we cloned the rat IRF-1 gene
       and functionally characterized the IRF-1 promoter. Upon transfection
       into Nb2 T cells, 1.7 kilobases (kb) of IRF-1 5'-flanking DNA linked to
       a chloramphenicol acetyl transferase (CAT) reporter gene mediated a
       30-fold induction of CAT enzyme activity in response to 24 h of PRL
       stimulation. Deletion mutants containing 1.3, 0.6, and 0.2 kb
       5'-flanking DNA were incrementally less transcriptionally active,
       although 0.2 kb still mediated a 12-fold induction by PRL. The sequence
       between 1.7 and -0.2 kb linked to a heterologous thymidine kinase
       promoter failed to respond to PRL stimulation, suggesting that the
       activity of upstream PRL response elements may require an interaction
       with promoter-proximal elements. By assaying CAT enzyme activity across
       a 24-h PRL induction time course, we were able to assign G1 vs. S phase
       PRL responses of the IRF-1 gene to different regions of the IRF-1
       5'-flanking and promoter DNA. The 0.2-kb IRF-CAT construct was induced
       by PRL stimulation during the G1 phase of the cell cycle. In contrast,
       the 1.7-kb IRF-CAT construct was inducible by PRL during both G1 and S
       phase of the cell cycle. Hence, the PRL-induced biphasic expression of
       the IRF-1 gene appears to be controlled by separate PRL-responsive
       elements: elements in the first 0.2 kb of the IRF-1 promoter region act
       during early activation, and elements between 0.2 and 1.7 kb act in
       concert with the proximal 0.2-kb region during S phase progression.
 DE    Animal  Base Sequence  Cell Cycle  Cell Line  Chloramphenicol
       Acetyltransferase/ANALYSIS/METABOLISM  Comparative Study
       DNA/ANALYSIS/GENETICS  DNA-Binding Proteins/*GENETICS  *Gene Expression
       Regulation  Genes, env/*PHYSIOLOGY  Genes, fos/GENETICS  Genes,
       myc/GENETICS  Genes, Immediate-Early  Genes, Reporter  *G1 Phase  Human
       Mice  Molecular Sequence Data  Ornithine Decarboxylase/GENETICS
       Phosphoproteins/*GENETICS  Prolactin/*GENETICS/PHYSIOLOGY  Promoter
       Regions (Genetics)/GENETICS  Rats  *S Phase  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  T-Lymphocytes/CYTOLOGY  Transcription
       Factors/GENETICS  Transcription, Genetic  Transfection  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).