Nuclear adaptor Ldb1 regulates a transcriptional program essential for the maintenance of hematopoietic stem cells

被引：85

作者：

Li, LiQi ^{[1
]}

Jothi, Raja ^{[2
]}

Cui, Kairong ^{[3
]}

Lee, Jan Y. ^{[1
]}

Cohen, Tsadok ^{[4
]}

Gorivodsky, Marat ^{[4
]}

Tzchori, Itai ^{[4
]}

Zhao, Yangu ^{[4
]}

Hayes, Sandra M. ^{[5
]}

Bresnick, Emery H. ^{[6
]}

Zhao, Keji ^{[3
]}

Westphal, Heiner ^{[4
]}

Love, Paul E. ^{[1
]}

机构：

[1] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA

[2] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA

[3] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA

[4] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mammalian Mol Genet, NIH, Bethesda, MD USA

[5] SUNY Upstate Med Univ, Dept Microbiol & Immunol, Syracuse, NY USA

[6] Univ Wisconsin, Sch Med & Publ Hlth, Paul Carbone Canc Ctr, Wisconsin Inst Med Res, Madison, WI USA

来源：

NATURE IMMUNOLOGY | 2011年 / 12卷 / 02期

基金：

美国国家卫生研究院;

关键词：

PROGENITOR CELLS; SELF-RENEWAL; PROTEIN LMO2; LEUKEMIA; MICE; IDENTIFICATION; EXPRESSION; COMPLEXES; DIFFERENTIATION; SCL/TAL1;

D O I：

10.1038/ni.1978

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The nuclear adaptor Ldb1 functions as a core component of multiprotein transcription complexes that regulate differentiation in diverse cell types. In the hematopoietic lineage, Ldb1 forms a complex with the non-DNA-binding adaptor Lmo2 and the transcription factors E2A, Scl and GATA-1 (or GATA-2). Here we demonstrate a critical and continuous requirement for Ldb1 in the maintenance of both fetal and adult mouse hematopoietic stem cells (HSCs). Deletion of Ldb1 in hematopoietic progenitors resulted in the downregulation of many transcripts required for HSC maintenance. Genome-wide profiling by chromatin immunoprecipitation followed by sequencing (ChIP-Seq) identified Ldb1 complex-binding sites at highly conserved regions in the promoters of genes involved in HSC maintenance. Our results identify a central role for Ldb1 in regulating the transcriptional program responsible for the maintenance of HSCs.

引用

页码：129 / U38

页数：9

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