Ikaros DNA-Binding Proteins as Integral Components of B Cell Developmental-Stage-Specific Regulatory Circuits
Ikaros DNA-binding proteins are critical for the development of lymphocytes and other hematopoietic lineages, but it remains unclear how they cooperate with other regulators of signaling and transcription to achieve ordered gene expression during development. Here, we show that Ikaros proteins regulate the pre-BCR component lambda5 in a stage-specific manner. In pre-BI cells, Ikaros modulated lambda5 expression in competition with the transcriptional activator EBF. This required Ikaros binding to the Igll1 (lambda5) promoter and was abolished either by mutation of the Ikaros DNA-binding domain or by deletion of a single Ikaros site from the Igll1 promoter. At the transition from the pre-BI to pre-BII stage, the expression of the Ikaros family member Aiolos was upregulated and required for the efficient silencing of Igll1. Aiolos expression was controlled by pre-BCR signals via the adaptor protein SLP-65. Thus, pre-BCR signaling regulates Aiolos and the silencing of Igll1 via a developmental-stage-specific feedback loop.
Ikaros DNA-Binding Proteins
as Integral Components of B Cell
Developmental-Stage-Speciﬁc Regulatory Circuits
Elizabeth C. Thompson, Bradley S. Cobb, Pierangela Sabbattini, Sonja Meixlsperger, Vania Parelho,
David Liberg, Benjamin Taylor, Niall Dillon, Katia Georgopoulos, Hassan Jumaa, Stephen T. Smale,
Amanda G. Fisher, and Matthias Merkenschlager
(Immunity 26, 335–344; March 2007)
In the version of this paper published originally online, the publication date was incorrectly listed as March 8, 2007. The
correct date is March 15, 2007. This has now been corrected online and in print, and we regret the error.
Immunity 26, 533, April 2007 ª2007 Elsevier Inc. 533