Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2
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- 1 June 2003
- journal article
- research article
- Published by Springer Nature in Nature Genetics
- Vol. 34 (3) , 308-312
- https://doi.org/10.1038/ng1170
Abstract
Mice lacking the transcriptional repressor oncoprotein Gfi1 are unexpectedly neutropenic1,2. We therefore screened GFI1 as a candidate for association with neutropenia in affected individuals without mutations in ELA2 (encoding neutrophil elastase), the most common cause of severe congenital neutropenia (SCN; ref. 3). We found dominant negative zinc finger mutations that disable transcriptional repressor activity. The phenotype also includes immunodeficient lymphocytes and production of a circulating population of myeloid cells that appear immature. We show by chromatin immunoprecipitation, gel shift, reporter assays and elevated expression of ELA2 in vivo in neutropenic individuals that GFI1 represses ELA2, linking these two genes in a common pathway involved in myeloid differentiation.Keywords
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