Journal article

Developmental and species-divergent globin switching are driven by BCL11A

Vijay G Sankaran, Jian Xu, Tobias Ragoczy, Gregory C Ippolito, Carl R Walkley, Shanna D Maika, Yuko Fujiwara, Masafumi Ito, Mark Groudine, MA Bender, Philip W Tucker, Stuart H Orkin

Nature | NATURE PUBLISHING GROUP | Published : 2009

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 beta-globin loci have served as a model for gene regulation during development. Transgenic mice containing the human beta-globin locus, consisting of the linked embryonic (epsilon), fetal (gamma) and adult (beta) 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 gamma-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..

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Grants

Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


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.