title: Nuclear adaptor Ldb1 regulates a transcriptional program essential for the maintenance of hematopoietic stem cells.
abstract: 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.
authors.affiliation: Section on Cellular & Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: LiQi
authors.initials: L
authors.lastname: Li
authors.forename: Raja
authors.initials: R
authors.lastname: Jothi
authors.forename: Kairong
authors.initials: K
authors.lastname: Cui
authors.forename: Jan Y
authors.initials: JY
authors.lastname: Lee
authors.forename: Tsadok
authors.initials: T
authors.lastname: Cohen
authors.forename: Marat
authors.initials: M
authors.lastname: Gorivodsky
authors.forename: Itai
authors.initials: I
authors.lastname: Tzchori
authors.forename: Yangu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Hayes
authors.forename: Emery H
authors.initials: EH
authors.lastname: Bresnick
authors.forename: Keji
authors.initials: K
authors.lastname: Zhao
authors.forename: Heiner
authors.initials: H
authors.lastname: Westphal
authors.forename: Paul E
authors.initials: PE
authors.lastname: Love
mesh_terms: D019264:Adoptive Transfer; D053687:Adult Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D005260:Female; D047109:Fetal Development / Q000235:genetics / Q000276:immunology; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D060588:LIM Domain Proteins; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011247:Pregnancy; D011485:Protein Binding; D050436:Regulatory Elements, Transcriptional / Q000235:genetics / Q000276:immunology; D015533:Transcriptional Activation / Q000235:genetics / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C102084:Ldb1 protein, mouse