| First Author | Begitt A | Year | 2014 |
| Journal | Nat Immunol | Volume | 15 |
| Issue | 2 | Pages | 168-76 |
| PubMed ID | 24413774 | Mgi Jnum | J:209388 |
| Mgi Id | MGI:5567047 | Doi | 10.1038/ni.2794 |
| Citation | Begitt A, et al. (2014) STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling. Nat Immunol 15(2):168-76 |
| abstractText | STAT1 is an indispensable component of a heterotrimer (ISGF3) and a STAT1 homodimer (GAF) that function as transcription regulators in type 1 and type 2 interferon signaling, respectively. To investigate the importance of STAT1-cooperative DNA binding, we generated gene-targeted mice expressing cooperativity-deficient STAT1 with alanine substituted for Phe77. Neither ISGF3 nor GAF bound DNA cooperatively in the STAT1F77A mouse strain, but type 1 and type 2 interferon responses were affected differently. Type 2 interferon-mediated transcription and antibacterial immunity essentially disappeared owing to defective promoter recruitment of GAF. In contrast, STAT1 recruitment to ISGF3 binding sites and type 1 interferon-dependent responses, including antiviral protection, remained intact. We conclude that STAT1 cooperativity is essential for its biological activity and underlies the cellular responses to type 2, but not type 1 interferon. |
