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

被引：176

作者：

Schwickert, Tanja A. ^{[1
]}

Tagoh, Hiromi ^{[1
]}

Gueltekin, Sinan ^{[1
]}

Dakic, Aleksandar ^{[1
]}

Axelsson, Elin ^{[1
]}

Minnich, Martina ^{[1
]}

Ebert, Anja ^{[1
]}

Werner, Barbara ^{[1
]}

Roth, Mareike ^{[1
]}

Cimmino, Luisa ^{[2
]}

Dickins, Ross A. ^{[2
]}

Zuber, Johannes ^{[1
]}

Jaritz, Markus ^{[1
]}

Busslinger, Meinrad ^{[1
]}

机构：

[1] Vienna Bioctr, Res Inst Mol Pathol, Vienna, Austria

[2] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia

来源：

NATURE IMMUNOLOGY | 2014年 / 15卷 / 03期

基金：

欧洲研究理事会;

关键词：

DNA-BINDING PROTEINS; LYMPHOBLASTIC-LEUKEMIA; EXCHANGE FACTOR; AIOLOS; GENE; REPRESSION; RECEPTOR; LINEAGE; CYCLE; RAC;

D O I：

10.1038/ni.2828

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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.

引用

页码：283 / 293

页数：11

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