Show simple item record

dc.contributor.authorAnguita, Eduardo
dc.contributor.authorHughes, Jim
dc.contributor.authorHeyworth, Clare M
dc.contributor.authorBlobel, Gerd A
dc.contributor.authorWood, William G
dc.contributor.authorHiggs, Douglas R
dc.date.accessioned2009-08-25T11:07:01Z
dc.date.available2009-08-25T11:07:01Z
dc.date.issued2004-07-21
dc.identifier.citationGlobin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2. 2004, 23 (14):2841-52 EMBO J.en
dc.identifier.issn0261-4189
dc.identifier.pmid15215894
dc.identifier.doi10.1038/sj.emboj.7600274
dc.identifier.urihttp://hdl.handle.net/10541/78444
dc.description.abstractHow does an emerging transcriptional programme regulate individual genes as stem cells undergo lineage commitment, differentiation and maturation? To answer this, we have analysed the dynamic protein/DNA interactions across 130 kb of chromatin containing the mouse alpha-globin cluster in cells representing all stages of differentiation from stem cells to mature erythroblasts. The alpha-gene cluster appears to be inert in pluripotent cells, but priming of expression begins in multipotent haemopoietic progenitors via GATA-2. In committed erythroid progenitors, GATA-2 is replaced by GATA-1 and binding is extended to additional sites including the alpha-globin promoters. Both GATA-1 and GATA-2 nucleate the binding of various protein complexes including SCL/LMO2/E2A/Ldb-1 and NF-E2. Changes in protein/DNA binding are accompanied by sequential alterations in long-range histone acetylation and methylation. The recruitment of polymerase II, which ultimately leads to a rapid increase in alpha-globin transcription, occurs late in maturation. These studies provide detailed evidence for the more general hypothesis that commitment and differentiation are primarily driven by the sequential appearance of key transcriptional factors, which bind chromatin at specific, high-affinity sites.
dc.language.isoenen
dc.subjectHaematopoiesisen
dc.subject.meshAcetylation
dc.subject.meshAnimals
dc.subject.meshBinding Sites
dc.subject.meshCell Differentiation
dc.subject.meshCell Lineage
dc.subject.meshChromatin
dc.subject.meshDNA Polymerase II
dc.subject.meshDNA-Binding Proteins
dc.subject.meshErythroid Precursor Cells
dc.subject.meshErythroid-Specific DNA-Binding Factors
dc.subject.meshGATA1 Transcription Factor
dc.subject.meshGATA2 Transcription Factor
dc.subject.meshGene Expression Regulation, Developmental
dc.subject.meshGlobins
dc.subject.meshHematopoiesis
dc.subject.meshHistones
dc.subject.meshL Cells (Cell Line)
dc.subject.meshMethylation
dc.subject.meshMice
dc.subject.meshModels, Biological
dc.subject.meshNF-E2 Transcription Factor
dc.subject.meshNF-E2 Transcription Factor, p45 Subunit
dc.subject.meshNuclear Proteins
dc.subject.meshPromoter Regions, Genetic
dc.subject.meshProteins
dc.subject.meshTranscription Factors
dc.subject.meshTranscriptional Activation
dc.subject.meshZinc Fingers
dc.titleGlobin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2.en
dc.typeArticleen
dc.contributor.departmentMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.en
dc.identifier.journalThe EMBO Journalen
html.description.abstractHow does an emerging transcriptional programme regulate individual genes as stem cells undergo lineage commitment, differentiation and maturation? To answer this, we have analysed the dynamic protein/DNA interactions across 130 kb of chromatin containing the mouse alpha-globin cluster in cells representing all stages of differentiation from stem cells to mature erythroblasts. The alpha-gene cluster appears to be inert in pluripotent cells, but priming of expression begins in multipotent haemopoietic progenitors via GATA-2. In committed erythroid progenitors, GATA-2 is replaced by GATA-1 and binding is extended to additional sites including the alpha-globin promoters. Both GATA-1 and GATA-2 nucleate the binding of various protein complexes including SCL/LMO2/E2A/Ldb-1 and NF-E2. Changes in protein/DNA binding are accompanied by sequential alterations in long-range histone acetylation and methylation. The recruitment of polymerase II, which ultimately leads to a rapid increase in alpha-globin transcription, occurs late in maturation. These studies provide detailed evidence for the more general hypothesis that commitment and differentiation are primarily driven by the sequential appearance of key transcriptional factors, which bind chromatin at specific, high-affinity sites.


This item appears in the following Collection(s)

Show simple item record