Section on Cellular & Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Nat Immunol. 2011 Feb;12(2):129-36. doi: 10.1038/ni.1978. Epub 2010 Dec 26.
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.
核衔接蛋白 Ldb1 作为调节多种细胞类型分化的多蛋白转录复合物的核心组成部分发挥作用。在造血谱系中，Ldb1 与非 DNA 结合衔接蛋白 Lmo2 和转录因子 E2A、Scl 和 GATA-1（或 GATA-2）形成复合物。在这里，我们证明了 Ldb1 在维持胎儿和成年小鼠造血干细胞（HSC）中的关键和持续需求。在造血祖细胞中删除 Ldb1 导致许多维持 HSC 所需的转录本下调。染色质免疫沉淀测序（ChIP-Seq）的全基因组分析鉴定了参与 HSC 维持的基因启动子中高度保守区域的 Ldb1 复合物结合位点。我们的研究结果确定了 Ldb1 在调节负责维持 HSCs 的转录程序中的核心作用。
