title: GABP transcription factor is required for myeloid differentiation, in part, through its control of Gfi-1 expression.
abstract: GABP is an ets transcription factor that regulates genes that are required for myeloid differentiation. The tetrameric GABP complex includes GABPα, which binds DNA via its ets domain, and GABPβ, which contains the transcription activation domain. To examine the role of GABP in myeloid differentiation, we generated mice in which Gabpa can be conditionally deleted in hematopoietic tissues. Gabpa knockout mice rapidly lost myeloid cells, and residual myeloid cells were dysplastic and immunophenotypically abnormal. Bone marrow transplantation demonstrated that Gabpα null cells could not contribute to the myeloid compartment because of cell intrinsic defects. Disruption of Gabpa was associated with a marked reduction in myeloid progenitor cells, and Gabpα null myeloid cells express reduced levels of the transcriptional repressor, Gfi-1. Gabp bound and activated the Gfi1 promoter, and transduction of Gabpa knockout bone marrow with Gfi1 partially rescued defects in myeloid colony formation and myeloid differentiation. We conclude that Gabp is required for myeloid differentiation due, in part, to its regulation of the tran-scriptional repressor Gfi-1.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Zhong-Fa
authors.initials: ZF
authors.lastname: Yang
authors.forename: Karen
authors.initials: K
authors.lastname: Drumea
authors.forename: James
authors.initials: J
authors.lastname: Cormier
authors.forename: Junling
authors.initials: J
authors.lastname: Wang
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhu
authors.forename: Alan G
authors.initials: AG
authors.lastname: Rosmarin
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D039481:CD11b Antigen / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D051268:GA-Binding Protein Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D055786:Gene Knockout Techniques; D051379:Mice; D018345:Mice, Knockout; D038042:Myelopoiesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D010641:Phenotype; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D039481:CD11b Antigen; D004268:DNA-Binding Proteins; D051268:GA-Binding Protein Transcription Factor; C495656:Gabpa protein, mouse; C079873:Gfi1 protein, mouse; D014157:Transcription Factors