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Nat Immunol. 2014 Mar;15(3):283-93. doi: 10.1038/ni.2828. Epub 2014 Feb 9.

Stage-specific control of early B cell development by the transcription factor Ikaros.

Author information

1
1] Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria. [2].
2
Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
3
The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.

Abstract

The transcription factor Ikaros is an essential regulator of lymphopoiesis. Here we studied its B cell-specific function by conditional inactivation of the gene encoding Ikaros (Ikzf1) in pro-B cells. B cell development was arrested at an aberrant 'pro-B cell' stage characterized by increased cell adhesion and loss of signaling via the pre-B cell signaling complex (pre-BCR). Ikaros activated genes encoding signal transducers of the pre-BCR and repressed genes involved in the downregulation of pre-BCR signaling and upregulation of the integrin signaling pathway. Unexpectedly, derepression of expression of the transcription factor Aiolos did not compensate for the loss of Ikaros in pro-B cells. Ikaros induced or suppressed active chromatin at regulatory elements of activated or repressed target genes. Notably, binding of Ikaros and expression of its target genes were dynamically regulated at distinct stages of early B lymphopoiesis.

PMID:
24509509
PMCID:
PMC5790181
DOI:
10.1038/ni.2828
[Indexed for MEDLINE]
Free PMC Article

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