A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate

被引：392

作者：

Lin, Yin C. ^{[2
]}

Jhunjhunwala, Suchit ^{[2
]}

Benner, Christopher ^{[1
]}

Heinz, Sven ^{[1
]}

Welinder, Eva ^{[2
,3
]}

Mansson, Robert ^{[2
]}

Sigvardsson, Mikael ^{[4
]}

Hagman, James ^{[5
]}

Espinoza, Celso A. ^{[6
]}

Dutkowski, Janusz ^{[1
,7
,8
]}

Ideker, Trey ^{[1
,7
,8
]}

Glass, Christopher K. ^{[1
]}

Murre, Cornelis ^{[2
]}

机构：

[1] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Mol Biol, La Jolla, CA 92093 USA

[3] Lund Univ, Ctr Stem Cell Biol & Cell Therapy, Lund, Sweden

[4] Linkoping Univ, Dept Biomed & Surg, Linkoping, Sweden

[5] Natl Jewish Hlth, Integrated Dept Immunol, Denver, CO USA

[6] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA

[7] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA

[8] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

来源：

NATURE IMMUNOLOGY | 2010年 / 11卷 / 07期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

LOOP-HELIX PROTEIN; CHROMATIN SIGNATURES; COMMITMENT; EXPRESSION; PTEN; PROLIFERATION; SPECIFICATION; CYTOSCAPE; ENHANCERS; DISTINCT;

D O I：

10.1038/ni.1891

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

It is now established that the transcription factors E2A, EBF1 and Foxo1 have critical roles in B cell development. Here we show that E2A and EBF1 bound regulatory elements present in the Foxo1 locus. E2A and EBF1, as well as E2A and Foxo1, in turn, were wired together by a vast spectrum of cis-regulatory sequences. These associations were dynamic during developmental progression. Occupancy by the E2A isoform E47 directly resulted in greater abundance, as well as a pattern of monomethylation of histone H3 at lysine 4 (H3K4) across putative enhancer regions. Finally, we divided the pro-B cell epigenome into clusters of loci with occupancy by E2A, EBF and Foxo1. From this analysis we constructed a global network consisting of transcriptional regulators, signaling and survival factors that we propose orchestrates B cell fate.

引用

页码：635 / U109

页数：10

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