Repression of Id2 expression by Gfi-1 is required for B-cell and myeloid development.
The development of mature blood cells from hematopoietic stem cells requires coordinated activities of transcriptional networks. Transcriptional repressor growth factor independence 1 (Gfi-1) is required for the development of B cells, T cells, neutrophils, and for the maintenance of hematopoietic stem cell function. However, the mechanisms by which Gfi-1 regulates hematopoiesis and how Gfi-1 integrates into transcriptional networks remain unclear. Here, we provide evidence that Id2 is a transcriptional target of Gfi-1, and repression of Id2 by Gfi-1 is required for B-cell and myeloid development. Gfi-1 binds to 3 conserved regions in the Id2 promoter and represses Id2 promoter activity in transient reporter assays. Increased Id2 expression was observed in multipotent progenitors, myeloid progenitors, T-cell progenitors, and B-cell progenitors in Gfi-1(-/-) mice. Knockdown of Id2 expression or heterozygosity at the Id2 locus partially rescues the B-cell and myeloid development but not the T-cell development in Gfi-1(-/-) mice. These studies demonstrate a role of Id2 in mediating Gfi-1 functions in B-cell and myeloid development and provide a direct link between Gfi-1 and the B-cell transcriptional network by its ability to repress Id2 expression.
Li
Huajie
H
Basic Research Program, SAIC-Frederick Inc, Center for Cancer Research, National Cancer Institute at Frederick, MD 21702, USA.
Ji
Ming
M
Klarmann
Kimberly D
KD
Keller
Jonathan R
JR
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D001483:Base Sequence; D015153:Blotting, Western; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D003114:Colony-Forming Units Assay; D004268:DNA-Binding Proteins / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D007124:Immunoenzyme Techniques; D051797:Inhibitor of Differentiation Protein 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000166:cytology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D014162:Transfection
D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D012333:RNA, Messenger; D014157:Transcription Factors; D008156:Luciferases
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