Ikaros represses the transcriptional response to Notch signaling in T-cell development.

ABSTRACT: Notch activity is essential for early T-cell differentiation, but aberrant activity induces T-cell transformation. Thus, Notch target genes must be efficiently silenced in cells where Notch activity is no longer required. How these genes are repressed remains poorly understood. We report here that the Ikaros transcription factor plays a crucial role in repressing the transcriptional response to Notch signaling in T-cell development. Using the Notch target gene Hes-1 as a model, we show that Ikaros and RBP-Jkappa, the transcriptional mediator of Notch signaling, compete for binding to two elements in the Hes-1 promoter in immature thymocytes. This antagonistic interaction likely occurs at the CD4(-) CD8(-) CD3(-) double-negative 4 (DN4) stage, where Ikaros levels and binding to the Hes-1 pr

SUBMITTER: Kleinmann E 

PROVIDER: S-EPMC2593445 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature