tailieunhanh - Báo cáo khoa học: Identification of GAS-dependent interferon-sensitive target genes whose transcription is STAT2-dependent but ISGF3-independent

Signal transducer and activator of transcription 2 (STAT2) is best known as a critical transactivator component of the interferon-stimulated gene factor 3 (ISGF3) complex that drives the expression of many interferon (IFN)-inducible genes. However, STAT2 is also involved in DNA binding in non-ISGF3 transcriptional complexes. | ềFEBS Journal Identification of GAS-dependent interferon-sensitive target genes whose transcription is STAT2-dependent but ISGF3-independent Melissa M. Brierley1 Katie L. Marchington1 Igor Jurisica2 and Eleanor N. Fish1 1 Department of Celland Molecular Biology Toronto GeneralResearch Institute University Health Network and Department of Immunology University of Toronto ON Canada 2 Division of Signaling Biology Ontario Cancer Institute University Health Network and Department of MedicalBiophysics University of Toronto ON Canada Keywords gene regulation interferon signal transduction transcription factors Correspondence E. N. Fish Toronto GeneralResearch Institute 67 College Street Rm 424 Toronto ON M5G 2M1 Canada Fax 1 416 340 3453 Tel 1 416 340 5380 E-mail Received 19 January 2006 revised 6 February 2006 accepted 13 February 2006 doi Signal transducer and activator of transcription 2 STAT2 is best known as a critical transactivator component of the interferon-stimulated gene factor 3 ISGF3 complex that drives the expression of many interferon IFN -inducible genes. However STAT2 is also involved in DNA binding in non-ISGF3 transcriptional complexes. We used a DNA microarray to survey the expression of genes regulated by IFN-inducible STAT2-depend-ent DNA binding and compared the cDNAs of IFN-treated cells overexpressing intact STAT2 to those of IFN-treated cells overexpressing mutated STAT2 lacking the DNA binding domain. The IFN-inducible expression of genes known to be regulated by ISGF3 was similar in both cases. However a subset of IFN-inducible genes was identified whose expression was decreased in cells expressing the mutated STAT2. Importantly these genes all contained gamma-activated sequence GAS -like elements in their 5 flanking sequences. Our data reveal the existence of a collection of GAS-regulated target genes whose expression is IFN-inducible and independent of ISGF3 but highly dependent on the .