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Prepublished online as a Blood First Edition Paper on August 14, 2003; DOI 10.1182/blood-2003-05-1540.
Submitted May 14, 2003
Accepted August 4, 2003
Developmental stage-specific epigenetic control of human beta globin gene expression is potentiated in hematopoietic progenitor cells prior to their transcriptional activation
Stefania Bottardi, Angelique Aumont, Frank Grosveld, and Eric Milot*
Faculty of Medicine, Guy-Bernier Research Centre, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, PQ, Canada
Department of Cell Biology and Genetics, Erasmus University Rotterdam, Faculty of Medicine, Rotterdam, The Netherlands
* Corresponding author; email: eric.milot{at}hmr.qc.ca.
To study epigenetic regulation of the human  -globin locus during hematopoiesis, we investigated patterns of histone modification and chromatin accessibility along this locus in hematopoietic progenitor cells (HPC) derived from both humans and transgenic mice. We demonstrate that the developmentally-related activation of human -like globin genes in humans and transgenic mice HPC is preceded by a wave of gene-specific histone H3 hyperacetylation and K4 dimethylation. In erythroid cells, expression of -like globin genes is associated with histone hyperacetylation along these genes and, surprisingly, with local deacetylation at active promoters. We also show that endogenous mouse major and human -like genes are subject to different epigenetic control mechanisms in HPC. This difference is likely due to intrinsic properties of the human -globin locus since, in transgenic mice, this locus is epigenetically regulated in the same manner as in human HPC. Our results suggest that a defined pattern of histone H3 acetylation/dimethylation is important for specific activation of human globin promoters during development in human and transgenic HPC. We propose that this transient chromatin acetylation/dimethylation is involved in gene-specific potentiation in HPC, i.e., before extensive chromatin remodelling and transcription take place in erythroid cells.
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