HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Interferon induction of gene transcription analyzed by in vivo footprinting.

Abstract
The promoters of two interferon-induced genes (the ISG54 and guanylate-binding protein [GBP] genes) have been analyzed in whole cells and in isolated nuclei by using a new genomic sequencing technique. The ISG54 gene contains an interferon-simulating response element (ISRE), earlier shown to be necessary and sufficient for alpha interferon (IFN-alpha) induction, that appeared complexed with proteins in both transcribing and nontranscribing cells. However, the extent of protection and hypersensitivity to DNase I or dimethyl sulfate within the ISRE region was changed upon transcriptional induction, suggesting the binding of different factors in different transcriptional states. In addition to the ISRE, the GBP gene needs a newly recognized DNA element, called the GAS, that partly overlaps the ISRE for full induction by either IFN-alpha or IFN-gamma. This GAS element was transiently protected against DNase I in the nuclei of interferon-treated cells but was not protected at later times when transcription reached maximal levels. Thus, the GAS-binding activity may be necessary only transiently for the initial assembly of a transcription initiation complex on the GBP promoter. Dimethyl sulfate methylation of genomic DNA performed on intact cells showed a characteristic sensitivity over the GAS that correlated with transcription levels and that persisted longer than did DNase I protection over the GAS. These results demonstrate the involvement of the GAS in IFN-alpha and -gamma induction of GBP and suggest the presence of an altered DNA conformation or a small protein in the major groove of the GAS associated with ongoing GBP transcription.
AuthorsJ Mirkovitch, T Decker, J E Darnell Jr
JournalMolecular and cellular biology (Mol Cell Biol) Vol. 12 Issue 1 Pg. 1-9 (Jan 1992) ISSN: 0270-7306 [Print] United States
PMID1729591 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Interferon-alpha
  • Sulfuric Acid Esters
  • Interferon-gamma
  • DNA
  • Deoxyribonuclease I
  • GTP-Binding Proteins
  • dimethyl sulfate
Topics
  • Base Sequence
  • Cell Line
  • DNA
  • Deoxyribonuclease I (metabolism)
  • GTP-Binding Proteins (genetics)
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Interferon-alpha (physiology)
  • Interferon-gamma (physiology)
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Regulatory Sequences, Nucleic Acid
  • Sulfuric Acid Esters (pharmacology)
  • TATA Box
  • Transcription, Genetic

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: