The C-terminal zinc finger of GATA-1 or GATA-2 is sufficient to induce megakaryocytic differentiation of an early myeloid cell line. (original) (raw)
- Journal List
- Mol Cell Biol
- v.15(2); 1995 Feb
- PMC231921
Mol Cell Biol. 1995 Feb; 15(2): 634–641.
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Abstract
The GATA-1 and GATA-2 transcription factors, which each contain two homologous zinc fingers, are important hematopoietic regulators expressed within the erythroid, mast cell, and megakaryocytic lineages. Enforced expression of either factor in the primitive myeloid line 416B induces megakaryocytic differentiation. The features of their structure required for this activity have been explored. The ability of 12 GATA-1 mutants to promote 416B maturation was compared with their DNA-binding activity and transactivation potential. Differentiation did not require any of the seven serine residues that are phosphorylated in vivo, an N-terminal region bearing the major transactivation domain, or a C-terminal segment beyond the fingers. Removal of a consensus nuclear localization signal following the second finger did not block differentiation or nuclear translocation. The N-terminal finger was also dispensable, although its removal attenuated differentiation. In contrast, the C-terminal finger was essential, underscoring its distinct function. Remarkably, only 69 residues spanning the C-terminal finger were required to induce limited megakaryocytic differentiation. Analysis of three GATA-2 mutants led to the same conclusion. Endogenous GATA-1 mRNA was induced by most mutants and may contribute to differentiation. Because the GATA-1 C-terminal finger could bind its target site but not transactivate a minimal reporter, it may direct megakaryocytic maturation by derepressing specific genes and/or by interacting with another protein which provides the transactivation function.
Full Text
The Full Text of this article is available as a PDF (399K).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arceci RJ, King AA, Simon MC, Orkin SH, Wilson DB. Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart. Mol Cell Biol. 1993 Apr;13(4):2235–2246. [PMC free article] [PubMed] [Google Scholar]
- Blobel GA, Simon MC, Orkin SH. Rescue of GATA-1-deficient embryonic stem cells by heterologous GATA-binding proteins. Mol Cell Biol. 1995 Feb;15(2):626–633. [PMC free article] [PubMed] [Google Scholar]
- Bowtell DD, Johnson GR, Kelso A, Cory S. Expression of genes transferred to haemopoietic stem cells by recombinant retroviruses. Mol Biol Med. 1987 Aug;4(4):229–250. [PubMed] [Google Scholar]
- Crossley M, Orkin SH. Phosphorylation of the erythroid transcription factor GATA-1. J Biol Chem. 1994 Jun 17;269(24):16589–16596. [PubMed] [Google Scholar]
- Crotta S, Nicolis S, Ronchi A, Ottolenghi S, Ruzzi L, Shimada Y, Migliaccio AR, Migliaccio G. Progressive inactivation of the expression of an erythroid transcriptional factor in GM- and G-CSF-dependent myeloid cell lines. Nucleic Acids Res. 1990 Dec 11;18(23):6863–6869. [PMC free article] [PubMed] [Google Scholar]
- Dexter TM, Allen TD, Scott D, Teich NM. Isolation and characterisation of a bipotential haematopoietic cell line. Nature. 1979 Feb 8;277(5696):471–474. [PubMed] [Google Scholar]
- Dorfman DM, Wilson DB, Bruns GA, Orkin SH. Human transcription factor GATA-2. Evidence for regulation of preproendothelin-1 gene expression in endothelial cells. J Biol Chem. 1992 Jan 15;267(2):1279–1285. [PubMed] [Google Scholar]
- Evans T, Felsenfeld G. The erythroid-specific transcription factor Eryf1: a new finger protein. Cell. 1989 Sep 8;58(5):877–885. [PubMed] [Google Scholar]
- Geisberg JV, Lee WS, Berk AJ, Ricciardi RP. The zinc finger region of the adenovirus E1A transactivating domain complexes with the TATA box binding protein. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2488–2492. [PMC free article] [PubMed] [Google Scholar]
- Ito E, Toki T, Ishihara H, Ohtani H, Gu L, Yokoyama M, Engel JD, Yamamoto M. Erythroid transcription factor GATA-1 is abundantly transcribed in mouse testis. Nature. 1993 Apr 1;362(6419):466–468. [PubMed] [Google Scholar]
- KARNOVSKY MJ, ROOTS L. A "DIRECT-COLORING" THIOCHOLINE METHOD FOR CHOLINESTERASES. J Histochem Cytochem. 1964 Mar;12:219–221. [PubMed] [Google Scholar]
- Ko LJ, Engel JD. DNA-binding specificities of the GATA transcription factor family. Mol Cell Biol. 1993 Jul;13(7):4011–4022. [PMC free article] [PubMed] [Google Scholar]
- Kudla B, Caddick MX, Langdon T, Martinez-Rossi NM, Bennett CF, Sibley S, Davies RW, Arst HN., Jr The regulatory gene areA mediating nitrogen metabolite repression in Aspergillus nidulans. Mutations affecting specificity of gene activation alter a loop residue of a putative zinc finger. EMBO J. 1990 May;9(5):1355–1364. [PMC free article] [PubMed] [Google Scholar]
- Lassar AB, Davis RL, Wright WE, Kadesch T, Murre C, Voronova A, Baltimore D, Weintraub H. Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Cell. 1991 Jul 26;66(2):305–315. [PubMed] [Google Scholar]
- Lee JS, Galvin KM, Shi Y. Evidence for physical interaction between the zinc-finger transcription factors YY1 and Sp1. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6145–6149. [PMC free article] [PubMed] [Google Scholar]
- Li L, Olson EN. Regulation of muscle cell growth and differentiation by the MyoD family of helix-loop-helix proteins. Adv Cancer Res. 1992;58:95–119. [PubMed] [Google Scholar]
- Luisi BF, Xu WX, Otwinowski Z, Freedman LP, Yamamoto KR, Sigler PB. Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature. 1991 Aug 8;352(6335):497–505. [PubMed] [Google Scholar]
- Martin DI, Zon LI, Mutter G, Orkin SH. Expression of an erythroid transcription factor in megakaryocytic and mast cell lineages. Nature. 1990 Mar 29;344(6265):444–447. [PubMed] [Google Scholar]
- Martin DI, Orkin SH. Transcriptional activation and DNA binding by the erythroid factor GF-1/NF-E1/Eryf 1. Genes Dev. 1990 Nov;4(11):1886–1898. [PubMed] [Google Scholar]
- Merika M, Orkin SH. DNA-binding specificity of GATA family transcription factors. Mol Cell Biol. 1993 Jul;13(7):3999–4010. [PMC free article] [PubMed] [Google Scholar]
- Natesan S, Gilman MZ. DNA bending and orientation-dependent function of YY1 in the c-fos promoter. Genes Dev. 1993 Dec;7(12B):2497–2509. [PubMed] [Google Scholar]
- Omichinski JG, Clore GM, Schaad O, Felsenfeld G, Trainor C, Appella E, Stahl SJ, Gronenborn AM. NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1. Science. 1993 Jul 23;261(5120):438–446. [PubMed] [Google Scholar]
- Orkin SH. GATA-binding transcription factors in hematopoietic cells. Blood. 1992 Aug 1;80(3):575–581. [PubMed] [Google Scholar]
- Pevny L, Simon MC, Robertson E, Klein WH, Tsai SF, D'Agati V, Orkin SH, Costantini F. Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature. 1991 Jan 17;349(6306):257–260. [PubMed] [Google Scholar]
- Rahuel C, Vinit MA, Lemarchandel V, Cartron JP, Roméo PH. Erythroid-specific activity of the glycophorin B promoter requires GATA-1 mediated displacement of a repressor. EMBO J. 1992 Nov;11(11):4095–4102. [PMC free article] [PubMed] [Google Scholar]
- Romeo PH, Prandini MH, Joulin V, Mignotte V, Prenant M, Vainchenker W, Marguerie G, Uzan G. Megakaryocytic and erythrocytic lineages share specific transcription factors. Nature. 1990 Mar 29;344(6265):447–449. [PubMed] [Google Scholar]
- Schwartzbauer G, Schlesinger K, Evans T. Interaction of the erythroid transcription factor cGATA-1 with a critical auto-regulatory element. Nucleic Acids Res. 1992 Sep 11;20(17):4429–4436. [PMC free article] [PubMed] [Google Scholar]
- Seto E, Lewis B, Shenk T. Interaction between transcription factors Sp1 and YY1. Nature. 1993 Sep 30;365(6445):462–464. [PubMed] [Google Scholar]
- Silver PA. How proteins enter the nucleus. Cell. 1991 Feb 8;64(3):489–497. [PubMed] [Google Scholar]
- Tapscott SJ, Davis RL, Thayer MJ, Cheng PF, Weintraub H, Lassar AB. MyoD1: a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts. Science. 1988 Oct 21;242(4877):405–411. [PubMed] [Google Scholar]
- Tsai SF, Martin DI, Zon LI, D'Andrea AD, Wong GG, Orkin SH. Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature. 1989 Jun 8;339(6224):446–451. [PubMed] [Google Scholar]
- Tsai SF, Strauss E, Orkin SH. Functional analysis and in vivo footprinting implicate the erythroid transcription factor GATA-1 as a positive regulator of its own promoter. Genes Dev. 1991 Jun;5(6):919–931. [PubMed] [Google Scholar]
- Visvader J, Adams JM. Megakaryocytic differentiation induced in 416B myeloid cells by GATA-2 and GATA-3 transgenes or 5-azacytidine is tightly coupled to GATA-1 expression. Blood. 1993 Sep 1;82(5):1493–1501. [PubMed] [Google Scholar]
- Visvader JE, Elefanty AG, Strasser A, Adams JM. GATA-1 but not SCL induces megakaryocytic differentiation in an early myeloid line. EMBO J. 1992 Dec;11(12):4557–4564. [PMC free article] [PubMed] [Google Scholar]
- Yamamoto M, Ko LJ, Leonard MW, Beug H, Orkin SH, Engel JD. Activity and tissue-specific expression of the transcription factor NF-E1 multigene family. Genes Dev. 1990 Oct;4(10):1650–1662. [PubMed] [Google Scholar]
- Yang HY, Evans T. Distinct roles for the two cGATA-1 finger domains. Mol Cell Biol. 1992 Oct;12(10):4562–4570. [PMC free article] [PubMed] [Google Scholar]
- Yang Z, Gu L, Romeo PH, Bories D, Motohashi H, Yamamoto M, Engel JD. Human GATA-3 trans-activation, DNA-binding, and nuclear localization activities are organized into distinct structural domains. Mol Cell Biol. 1994 Mar;14(3):2201–2212. [PMC free article] [PubMed] [Google Scholar]
Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis