Show simple item record

dc.contributor.authorChan, Wan Y I
dc.contributor.authorFollows, George A
dc.contributor.authorLacaud, Georges
dc.contributor.authorPimanda, John E
dc.contributor.authorLandry, Josette-Renee
dc.contributor.authorKinston, Sarah
dc.contributor.authorKnezevic, Kathy
dc.contributor.authorPiltz, Sandie
dc.contributor.authorDonaldson, Ian J
dc.contributor.authorGambardella, Laure
dc.contributor.authorSablitzky, Fred
dc.contributor.authorGreen, Anthony R
dc.contributor.authorKouskoff, Valerie
dc.contributor.authorGöttgens, Berthold
dc.date.accessioned2009-06-12T13:54:28Z
dc.date.available2009-06-12T13:54:28Z
dc.date.issued2007-03-01
dc.identifier.citationThe paralogous hematopoietic regulators Lyl1 and Scl are coregulated by Ets and GATA factors, but Lyl1 cannot rescue the early Scl-/- phenotype. 2007, 109 (5):1908-16 Blooden
dc.identifier.issn0006-4971
dc.identifier.pmid17053063
dc.identifier.doi10.1182/blood-2006-05-023226
dc.identifier.urihttp://hdl.handle.net/10541/70325
dc.description.abstractTranscription factors are key regulators of hematopoietic stem cells (HSCs), yet the molecular mechanisms that control their expression are largely unknown. Previously, we demonstrated that expression of Scl/Tal1, a transcription factor required for the specification of HSCs, is controlled by Ets and GATA factors. Here we characterize the molecular mechanisms controlling expression of Lyl1, a paralog of Scl also required for HSC function. Two closely spaced promoters directed expression to hematopoietic progenitor, megakaryocytic, and endothelial cells in transgenic mice. Conserved binding sites required for promoter activity were bound in vivo by GATA-2 and the Ets factors Fli1, Elf1, Erg, and PU.1. However, despite coregulation of Scl and Lyl1 by the same Ets and GATA factors, Scl expression was initiated prior to Lyl1 in embryonic stem (ES) cell differentiation assays. Moreover, ectopic expression of Scl but not Lyl1 rescued hematopoietic differentiation in Scl-/- ES cells, thus providing a molecular explanation for the vastly different phenotypes of Scl-/- and Lyl1-/- mouse embryos. Furthermore, coregulation of Scl and Lyl1 later during development may explain the mild phenotype of Scl-/- adult HSCs.
dc.language.isoenen
dc.subjectCancer Proteinsen
dc.subject.meshAmino Acid Sequence
dc.subject.meshAnimals
dc.subject.meshBase Sequence
dc.subject.meshBasic Helix-Loop-Helix Transcription Factors
dc.subject.meshCell Line
dc.subject.meshConserved Sequence
dc.subject.meshEmbryo, Mammalian
dc.subject.meshEndothelial Cells
dc.subject.meshGATA2 Transcription Factor
dc.subject.meshGene Expression
dc.subject.meshHematopoiesis
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshMice, Knockout
dc.subject.meshMolecular Sequence Data
dc.subject.meshNeoplasm Proteins
dc.subject.meshPhenotype
dc.subject.meshPromoter Regions, Genetic
dc.subject.meshProto-Oncogene Protein c-ets-1
dc.subject.meshProto-Oncogene Proteins
dc.subject.meshSequence Alignment
dc.subject.meshTime Factors
dc.titleThe paralogous hematopoietic regulators Lyl1 and Scl are coregulated by Ets and GATA factors, but Lyl1 cannot rescue the early Scl-/- phenotype.en
dc.typeArticleen
dc.contributor.departmentDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, United Kingdom.en
dc.identifier.journalBlooden
html.description.abstractTranscription factors are key regulators of hematopoietic stem cells (HSCs), yet the molecular mechanisms that control their expression are largely unknown. Previously, we demonstrated that expression of Scl/Tal1, a transcription factor required for the specification of HSCs, is controlled by Ets and GATA factors. Here we characterize the molecular mechanisms controlling expression of Lyl1, a paralog of Scl also required for HSC function. Two closely spaced promoters directed expression to hematopoietic progenitor, megakaryocytic, and endothelial cells in transgenic mice. Conserved binding sites required for promoter activity were bound in vivo by GATA-2 and the Ets factors Fli1, Elf1, Erg, and PU.1. However, despite coregulation of Scl and Lyl1 by the same Ets and GATA factors, Scl expression was initiated prior to Lyl1 in embryonic stem (ES) cell differentiation assays. Moreover, ectopic expression of Scl but not Lyl1 rescued hematopoietic differentiation in Scl-/- ES cells, thus providing a molecular explanation for the vastly different phenotypes of Scl-/- and Lyl1-/- mouse embryos. Furthermore, coregulation of Scl and Lyl1 later during development may explain the mild phenotype of Scl-/- adult HSCs.


This item appears in the following Collection(s)

Show simple item record