Globin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2.

2.50
Hdl Handle:
http://hdl.handle.net/10541/78444
Title:
Globin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2.
Authors:
Anguita, Eduardo; Hughes, Jim; Heyworth, Clare M; Blobel, Gerd A; Wood, William G; Higgs, Douglas R
Abstract:
How 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.
Affiliation:
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Citation:
Globin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2. 2004, 23 (14):2841-52 EMBO J.
Journal:
The EMBO Journal
Issue Date:
21-Jul-2004
URI:
http://hdl.handle.net/10541/78444
DOI:
10.1038/sj.emboj.7600274
PubMed ID:
15215894
Type:
Article
Language:
en
ISSN:
0261-4189
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
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.en
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
All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.