Globin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2.
AffiliationMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
MetadataShow full item record
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.
CitationGlobin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2. 2004, 23 (14):2841-52 EMBO J.
JournalThe EMBO Journal
- A major role for the TATA box in recruitment of chromatin modifying complexes to a globin gene promoter.
- Authors: Gui CY, Dean A
- Issue date: 2003 Jun 10
- Regulation of lineage restricted haemopoietic transcription factors in cell hybrids.
- Authors: Murrell AM, Green AR
- Issue date: 1995 Feb 16
- Lineage-restricted regulation of the murine SCL/TAL-1 promoter.
- Authors: Bockamp EO, McLaughlin F, Murrell AM, Göttgens B, Robb L, Begley CG, Green AR
- Issue date: 1995 Aug 15
- Essential role of NF-E2 in remodeling of chromatin structure and transcriptional activation of the epsilon-globin gene in vivo by 5' hypersensitive site 2 of the beta-globin locus control region.
- Authors: Gong QH, McDowell JC, Dean A
- Issue date: 1996 Nov
- Hematopoietic-specific activators establish an overlapping pattern of histone acetylation and methylation within a mammalian chromatin domain.
- Authors: Kiekhaefer CM, Grass JA, Johnson KD, Boyer ME, Bresnick EH
- Issue date: 2002 Oct 29