Journal article
Developmental and species-divergent globin switching are driven by BCL11A
VG Sankaran, J Xu, T Ragoczy, GC Ippolito, CR Walkley, SD Maika, Y Fujiwara, M Ito, M Groudine, MA Bender, PW Tucker, SH Orkin
Nature | NATURE PORTFOLIO | Published : 2009
DOI: 10.1038/nature08243
Abstract
The contribution of changes in cis-regulatory elements or trans-acting factors to interspecies differences in gene expression is not well understood. The mammalian β-globin loci have served as a model for gene regulation during development. Transgenic mice containing the human β-globin locus, consisting of the linked embryonic (ε), fetal (γ) and adult (β) genes, have been used as a system to investigate the temporal switch from fetal to adult haemoglobin, as occurs in humans. Here we show that the human γ-globin (HBG) genes in these mice behave as murine embryonic globin genes, revealing a limitation of the model and demonstrating that critical differences in the trans-acting milieu have ari..
View full abstractGrants
Awarded by National Institutes of Health
Funding Acknowledgements
We are grateful to K. Peterson and H. Fedosyuk for providing beta-locus mice, K. Gaensler for the A20 and A85 strains of b- locus mice, and T. Jacks for providing the K- RasG12D mice. We thank J. Palis and P. Kingsley for providing mouse embryonic globin antibodies, H. Mikkola and B. Van Handel for providing sorted human samples, and R. Byron and A. Telling for technical support. Wethank L. Zon, K. McGrath, P. Kingsley, J. Palis, M. Kowalczyk and T. Menne for advice and discussions. This work was supported by funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) (S.H.O. and M. G.) and the National Cancer Institute ( P. W. T.). S. H. O. is an Investigator of the Howard Hughes Medical Institute (HHMI). C. R. W. is a special fellow of the Leukemia & Lymphoma Society. T. R. is supported by a fellowship from the American Society of Hematology. J. X. is an HHMI fellow of the Helen Hay Whitney Foundation. V. G. S. is supported by a Medical Scientist Training Program Award from the NIH and G. C. I. is supported by a NCI postdoctoral fellowship.