| First Author | Harris MB | Year | 2005 |
| Journal | J Biol Chem | Volume | 280 |
| Issue | 13 | Pages | 13114-21 |
| PubMed ID | 15659391 | Mgi Jnum | J:98563 |
| Mgi Id | MGI:3578694 | Doi | 10.1074/jbc.M412649200 |
| Citation | Harris MB, et al. (2005) Repression of an interleukin-4-responsive promoter requires cooperative BCL-6 function. J Biol Chem 280(13):13114-21 |
| abstractText | BCL-6 functions as a potent transcriptional repressor that binds with specificity to DNA elements bearing marked similarity to STAT recognition sequences. Previous studies have demonstrated that BCL-6 and Stat6 can both bind and regulate the Iepsilon promoter that controls immunoglobulin heavy chain class switching to IgE. Examination of BCL-6-/- and BCL-6-/-Stat6-/- mice has demonstrated that BCL-6 is a repressor of IgE and that Stat6 is still required for the interleukin-4 (IL-4) induction of class switching to IgE in B cells lacking BCL-6. To define the mechanisms by which BCL-6 represses IL-4 function, we analyzed the role of BCL-6 in repressing the Iepsilon promoter. There are three BCL-6-binding sites within this IL-4-responsive promoter. Analysis of Iepsilon promoters that have mutated BCL-6-binding sites demonstrates that at least two of these sites are required for maximal BCL-6 repression of this locus. Footprinting analysis demonstrates that BCL-6 binds cooperatively to the two upstream binding sites in the Iepsilon promoter. This cooperative binding requires the POZ domain of BCL-6. Furthermore, activated Stat6 molecules can displace BCL-6 from one of these binding sites. These data demonstrate that cooperative interaction between BCL-6 molecules is required for repression of the Iepsilon promoter. |
