title: Transcriptional regulation of FHL1 by TLX1/HOX11 is dosage, cell-type and promoter context-dependent.
abstract: TLX1/HOX11 encodes an NK-like homeodomain transcription factor that is both normally required for embryonic development and aberrantly expressed in T-cell acute lymphoblastic leukemia. Previous studies have shown that TLX1 can regulate target genes including ALDH1A1 and FHL1. However, whereas ALDH1A1 is consistently regulated by TLX1, endogenous FHL1 is only induced in a proportion of fibroblast or T-cell clones stably expressing TLX1. Here, we provide an explanation for these findings by demonstrating that the induction of FHL1, but not ALDH1A1, requires a high level of TLX1 expression in NIH 3T3 cells. In luciferase reporter assays, TLX1-mediated repression rather than activation of the FHL1 gene promoter and the magnitude of this effect was strongly influenced by the cellular background. Together, these results characterize TLX1 as a dual function regulator whose activity in respect to FHL1 is critically dependent upon its cellular concentration, as well as cell type and promoter context.
authors: School of Veterinary and Biomedical Sciences, Division of Health Sciences, Murdoch University, Perth, WA 6150, Australia.
authors: Kim L
authors: KL
authors: Rice
authors: Ursula R
authors: UR
authors: Kees
authors: Wayne K
authors: WK
authors: Greene
mesh_terms: D024506:5' Flanking Region; D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D060588:LIM Domain Proteins; D051379:Mice; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D011960:Receptors, Estrogen / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D050697:Retinal Dehydrogenase; D016415:Sequence Alignment; D014162:Transfection
chemical_list: C101149:FHL1 protein, human; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; C071250:TLX1 protein, human; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase