title: Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism.
abstract: Gfi-1 and Gfi-1B can repress transcription and play important roles in hematopoietic cell survival and differentiation. Although these proteins are known to bind DNA through a C-terminal zinc-finger domain and may require an N-terminal SNAG domain (SNAIL/Gfi-1) to repress transcription, the mechanism by which Gfi-1 and Gfi-1B act is unknown. A first step towards understanding the mechanism by which these proteins repress transcription is to identify interacting proteins that could contribute to transcriptional repression. ETO (also termed MTG8), was first identified through its involvement in the (8;21) translocation associated with acute myelogenous leukemia. It attaches to the nuclear matrix and associates with histone deacetylases and the co-repressors N-CoR, SMRT, and mSin3A, and may act as a co-repressor for site-specific transcriptions factors. In this report we demonstrate that Gfi-1 interacts with ETO and related proteins both in vitro and in vivo and with histone deacetylase proteins in vivo. We observed that a portion of Gfi-1 and Gfi-1B associated with the nuclear matrix, as is the case with ETO. Moreover, Gfi-1 and ETO co-localize to punctate subnuclear structures. When co-expressed in mammalian cells, Gfi-1 associates with histone deacetylse-1 (HDAC-1), HDAC-2, and HDAC-3. These data identify ETO as a partner for Gfi-1 and Gfi-1B, and suggest that Gfi-1 proteins repress transcription through recruitment of histone deacetylase-containing complexes.
authors.affiliation: The Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Highway, Shreveport, LA 71130, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: McGhee
authors.forename: Josh
authors.initials: J
authors.lastname: Bryan
authors.forename: Liza
authors.initials: L
authors.lastname: Elliott
authors.forename: H Leighton
authors.initials: HL
authors.lastname: Grimes
authors.forename: Avedis
authors.initials: A
authors.lastname: Kazanjian
authors.forename: J Nathan
authors.initials: JN
authors.lastname: Davis
authors.forename: Shari
authors.initials: S
authors.lastname: Meyers
mesh_terms: D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D017930:Genes, Reporter / Q000235:genetics; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000378:metabolism* / Q000494:pharmacology; D007382:Intermediate Filaments / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D015530:Nuclear Matrix / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D000075142:RUNX1 Translocation Partner 1 Protein; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C498275:GFI1 protein, human; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D008164:Luminescent Proteins; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C082222:RUNX1T1 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; C012589:trichostatin A; D006655:Histone Deacetylases