Skip to Main content Skip to Navigation
Journal articles

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 promoter increase sharply and wild-type thymocytes lose their capacity to transcribe Hes-1 upon Notch stimulation. Nonresponsiveness to Notch signaling requires Ikaros, as Ikaros-deficient DN4 and CD4(+) CD8(+) double-positive (DP) cells remain competent to express Hes-1 after Notch activation. Further, Hes-1 promoter sequences from Ikaros-deficient DP cells show reduced trimethylated H3K27, a modification associated with silent chromatin. These results indicate that Ikaros functions as a transcriptional checkpoint to repress Notch target gene expression in T cells.
Document type :
Journal articles
Complete list of metadatas

https://www.hal.inserm.fr/inserm-00350904
Contributor : Maité Peney <>
Submitted on : Wednesday, January 7, 2009 - 5:30:46 PM
Last modification on : Thursday, April 23, 2020 - 2:26:26 PM

Links full text

Identifiers

Collections

Citation

Eva Kleinmann, Anne-Solen Geimer Le Lay, Maclean Sellars, Philippe Kastner, Susan Chan. Ikaros represses the transcriptional response to notch signaling in T-cell development.. Molecular and Cellular Biology, American Society for Microbiology, 2008, 28 (24), pp.7465-75. ⟨10.1128/MCB.00715-08⟩. ⟨inserm-00350904⟩

Share

Metrics

Record views

506