Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells.
Growth factor independence-1 (GFI1) and GFI1B are closely related, yet differentially expressed transcriptional repressors with nearly identical DNA binding domains. GFI1 is upregulated in the earliest thymocyte precursors, while GFI1B expression is restricted to T lymphopoiesis stages coincident with activation. Transgenic expression of GFI1 potentiates T-cell activation, while forced GFI1B expression decreases activation. Both mice and humans with mutant Gfi1 display lymphoid abnormalities. Here we describe autoregulation of Gfi1 in primary mouse thymocytes and a human T-cell line. GFI1 binding to cis-element sequences conserved between rat, mouse and human Gfi1 mediates direct and potent transcriptional repression. In addition, dramatic regulation of Gfi1 can also be mediated by GFI1B. These data provide the first example of a gene directly targeted by GFI1 and GFI1B. Moreover, they support a role for auto- and trans-regulation of Gfi1 by GFI1 and GFI1B in maintaining the normal expression patterns of Gfi1, and suggest that GFI1B may indirectly affect T-cell activation through repression of Gfi1.
Doan
Loretta L
LL
Institute for Cellular Therapeutics, University of Louisville, KY, USA.
Porter
Susan D
SD
Duan
Zhijun
Z
Flubacher
Marcella M
MM
Montoya
Diego
D
Tsichlis
Philip N
PN
Horwitz
Marshall
M
Gilks
C Blake
CB
Grimes
H Leighton
HL
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D017124:Conserved Sequence / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C498275:GFI1 protein, human; C111977:GFI1B protein, human; C079873:Gfi1 protein, mouse; C498276:Gfi1 protein, rat; C486395:Gfi1b protein, mouse; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA