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Mol Cell Biol. 1996 Nov; 16(11): 6083–6095.
doi: 10.1128/mcb.16.11.6083
PMCID: PMC231611
PMID: 8887638

Bach proteins belong to a novel family of BTB-basic leucine zipper transcription factors that interact with MafK and regulate transcription through the NF-E2 site.

T Oyake, K Itoh, H Motohashi, N Hayashi, H Hoshino, M Nishizawa, M Yamamoto, and K Igarashi
Author information Copyright and License information PMC Disclaimer

Abstract

Members of the small Maf family (MafK, MafF, and MafG) are basic region leucine zipper (bZip) proteins that can function as transcriptional activators or repressors. The dimer compositions of their DNA binding forms determine whether the small Maf family proteins activate or repress transcription. Using a yeast two-hybrid screen with a GAL4-MafK fusion protein, we have identified two novel bZip transcription factors, Bach1 and Bach2, as heterodimerization partners of MafK. In addition to a Cap'n'collar-type bZip domain, these Bach proteins possess a BTB domain which is a protein interaction motif; Bach1 and Bach2 show significant similarity to each other in these regions but are otherwise divergent. Whereas expression of Bach1 appears ubiquitous, that of Bach2 is restricted to monocytes and neuronal cells. Bach proteins bind in vitro to NF-E2 binding sites, recognition elements for the hematopoietic transcription factor NF-E2, by forming heterodimers with MafK. Furthermore, a DNA binding complex that contained MafK as well as Bach2 or a protein related closely to Bach2 was found to be present in mouse brain cells. Bach1 and Bach2 function as transcription repressors in transfection assays using fibroblast cells, but they function as a transcriptional activator and repressor, respectively, in cultured erythroid cells. The results suggest that members of the Bach family play important roles in coordinating transcription activation and repression by MafK.

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Selected References

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  • Andrews NC, Erdjument-Bromage H, Davidson MB, Tempst P, Orkin SH. Erythroid transcription factor NF-E2 is a haematopoietic-specific basic-leucine zipper protein. Nature. 1993 Apr 22;362(6422):722–728. [PubMed] [Google Scholar]
  • Andrews NC, Faller DV. A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. Nucleic Acids Res. 1991 May 11;19(9):2499–2499. [PMC free article] [PubMed] [Google Scholar]
  • Andrews NC, Kotkow KJ, Ney PA, Erdjument-Bromage H, Tempst P, Orkin SH. The ubiquitous subunit of erythroid transcription factor NF-E2 is a small basic-leucine zipper protein related to the v-maf oncogene. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11488–11492. [PMC free article] [PubMed] [Google Scholar]
  • Bardwell VJ, Treisman R. The POZ domain: a conserved protein-protein interaction motif. Genes Dev. 1994 Jul 15;8(14):1664–1677. [PubMed] [Google Scholar]
  • Beug H, Palmieri S, Freudenstein C, Zentgraf H, Graf T. Hormone-dependent terminal differentiation in vitro of chicken erythroleukemia cells transformed by ts mutants of avian erythroblastosis virus. Cell. 1982 Apr;28(4):907–919. [PubMed] [Google Scholar]
  • Caterina JJ, Ciavatta DJ, Donze D, Behringer RR, Townes TM. Multiple elements in human beta-globin locus control region 5' HS 2 are involved in enhancer activity and position-independent, transgene expression. Nucleic Acids Res. 1994 Mar 25;22(6):1006–1011. [PMC free article] [PubMed] [Google Scholar]
  • Caterina JJ, Donze D, Sun CW, Ciavatta DJ, Townes TM. Cloning and functional characterization of LCR-F1: a bZIP transcription factor that activates erythroid-specific, human globin gene expression. Nucleic Acids Res. 1994 Jun 25;22(12):2383–2391. [PMC free article] [PubMed] [Google Scholar]
  • Chan JY, Han XL, Kan YW. Isolation of cDNA encoding the human NF-E2 protein. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11366–11370. [PMC free article] [PubMed] [Google Scholar]
  • Chan JY, Han XL, Kan YW. Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11371–11375. [PMC free article] [PubMed] [Google Scholar]
  • Chen W, Zollman S, Couderc JL, Laski FA. The BTB domain of bric à brac mediates dimerization in vitro. Mol Cell Biol. 1995 Jun;15(6):3424–3429. [PMC free article] [PubMed] [Google Scholar] Retracted
  • Chen Z, Brand NJ, Chen A, Chen SJ, Tong JH, Wang ZY, Waxman S, Zelent A. Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO J. 1993 Mar;12(3):1161–1167. [PMC free article] [PubMed] [Google Scholar]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed] [Google Scholar]
  • Cordes SP, Barsh GS. The mouse segmentation gene kr encodes a novel basic domain-leucine zipper transcription factor. Cell. 1994 Dec 16;79(6):1025–1034. [PubMed] [Google Scholar]
  • DiBello PR, Withers DA, Bayer CA, Fristrom JW, Guild GM. The Drosophila Broad-Complex encodes a family of related proteins containing zinc fingers. Genetics. 1991 Oct;129(2):385–397. [PMC free article] [PubMed] [Google Scholar]
  • Dorn R, Krauss V, Reuter G, Saumweber H. The enhancer of position-effect variegation of Drosophila, E(var)3-93D, codes for a chromatin protein containing a conserved domain common to several transcriptional regulators. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11376–11380. [PMC free article] [PubMed] [Google Scholar]
  • DUNN TB, POTTER M. A transplantable mast-cell neoplasm in the mouse. J Natl Cancer Inst. 1957 Apr;18(4):587–601. [PubMed] [Google Scholar]
  • Farkas G, Gausz J, Galloni M, Reuter G, Gyurkovics H, Karch F. The Trithorax-like gene encodes the Drosophila GAGA factor. Nature. 1994 Oct 27;371(6500):806–808. [PubMed] [Google Scholar]
  • Fields S, Song O. A novel genetic system to detect protein-protein interactions. Nature. 1989 Jul 20;340(6230):245–246. [PubMed] [Google Scholar]
  • Forrester WC, Thompson C, Elder JT, Groudine M. A developmentally stable chromatin structure in the human beta-globin gene cluster. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1359–1363. [PMC free article] [PubMed] [Google Scholar]
  • Fujita H, Yamamoto M, Yamagami T, Hayashi N, Sassa S. Erythroleukemia differentiation. Distinctive responses of the erythroid-specific and the nonspecific delta-aminolevulinate synthase mRNA. J Biol Chem. 1991 Sep 15;266(26):17494–17502. [PubMed] [Google Scholar]
  • Fujiwara KT, Kataoka K, Nishizawa M. Two new members of the maf oncogene family, mafK and mafF, encode nuclear b-Zip proteins lacking putative trans-activator domain. Oncogene. 1993 Sep;8(9):2371–2380. [PubMed] [Google Scholar]
  • Gerasimova TI, Gdula DA, Gerasimov DV, Simonova O, Corces VG. A Drosophila protein that imparts directionality on a chromatin insulator is an enhancer of position-effect variegation. Cell. 1995 Aug 25;82(4):587–597. [PubMed] [Google Scholar]
  • Giniger E, Tietje K, Jan LY, Jan YN. lola encodes a putative transcription factor required for axon growth and guidance in Drosophila. Development. 1994 Jun;120(6):1385–1398. [PubMed] [Google Scholar]
  • Godt D, Couderc JL, Cramton SE, Laski FA. Pattern formation in the limbs of Drosophila: bric à brac is expressed in both a gradient and a wave-like pattern and is required for specification and proper segmentation of the tarsus. Development. 1993 Nov;119(3):799–812. [PubMed] [Google Scholar]
  • Grosveld F, van Assendelft GB, Greaves DR, Kollias G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 1987 Dec 24;51(6):975–985. [PubMed] [Google Scholar]
  • Harrison SD, Travers AA. The tramtrack gene encodes a Drosophila finger protein that interacts with the ftz transcriptional regulatory region and shows a novel embryonic expression pattern. EMBO J. 1990 Jan;9(1):207–216. [PMC free article] [PubMed] [Google Scholar]
  • Hu S, Fambrough D, Atashi JR, Goodman CS, Crews ST. The Drosophila abrupt gene encodes a BTB-zinc finger regulatory protein that controls the specificity of neuromuscular connections. Genes Dev. 1995 Dec 1;9(23):2936–2948. [PubMed] [Google Scholar]
  • Ichikawa Y. Differentiation of a cell line of myeloid leukemia. J Cell Physiol. 1969 Dec;74(3):223–234. [PubMed] [Google Scholar]
  • Igarashi K, Itoh K, Motohashi H, Hayashi N, Matuzaki Y, Nakauchi H, Nishizawa M, Yamamoto M. Activity and expression of murine small Maf family protein MafK. J Biol Chem. 1995 Mar 31;270(13):7615–7624. [PubMed] [Google Scholar]
  • Igarashi K, Itoh K, Hayashi N, Nishizawa M, Yamamoto M. Conditional expression of the ubiquitous transcription factor MafK induces erythroleukemia cell differentiation. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7445–7449. [PMC free article] [PubMed] [Google Scholar]
  • Igarashi K, Kataoka K, Itoh K, Hayashi N, Nishizawa M, Yamamoto M. Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins. Nature. 1994 Feb 10;367(6463):568–572. [PubMed] [Google Scholar]
  • Itoh K, Igarashi K, Hayashi N, Nishizawa M, Yamamoto M. Cloning and characterization of a novel erythroid cell-derived CNC family transcription factor heterodimerizing with the small Maf family proteins. Mol Cell Biol. 1995 Aug;15(8):4184–4193. [PMC free article] [PubMed] [Google Scholar]
  • Jiménez G, Griffiths SD, Ford AM, Greaves MF, Enver T. Activation of the beta-globin locus control region precedes commitment to the erythroid lineage. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10618–10622. [PMC free article] [PubMed] [Google Scholar]
  • Kataoka K, Fujiwara KT, Noda M, Nishizawa M. MafB, a new Maf family transcription activator that can associate with Maf and Fos but not with Jun. Mol Cell Biol. 1994 Nov;14(11):7581–7591. [PMC free article] [PubMed] [Google Scholar]
  • Kataoka K, Igarashi K, Itoh K, Fujiwara KT, Noda M, Yamamoto M, Nishizawa M. Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF-E2 transcription factor. Mol Cell Biol. 1995 Apr;15(4):2180–2190. [PMC free article] [PubMed] [Google Scholar]
  • Kataoka K, Noda M, Nishizawa M. Maf nuclear oncoprotein recognizes sequences related to an AP-1 site and forms heterodimers with both Fos and Jun. Mol Cell Biol. 1994 Jan;14(1):700–712. [PMC free article] [PubMed] [Google Scholar]
  • Kataoka K, Noda M, Nishizawa M. Transactivation activity of Maf nuclear oncoprotein is modulated by Jun, Fos and small Maf proteins. Oncogene. 1996 Jan 4;12(1):53–62. [PubMed] [Google Scholar]
  • Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–241. [PMC free article] [PubMed] [Google Scholar]
  • Kurschner C, Morgan JI. The maf proto-oncogene stimulates transcription from multiple sites in a promoter that directs Purkinje neuron-specific gene expression. Mol Cell Biol. 1995 Jan;15(1):246–254. [PMC free article] [PubMed] [Google Scholar]
  • Lim KC, Ishihara H, Riddle RD, Yang Z, Andrews N, Yamamoto M, Engel JD. Structure and regulation of the chicken erythroid delta-aminolevulinate synthase gene. Nucleic Acids Res. 1994 Apr 11;22(7):1226–1233. [PMC free article] [PubMed] [Google Scholar]
  • Liu Q, Ji X, Breitman ML, Hitchcock PF, Swaroop A. Expression of the bZIP transcription factor gene Nrl in the developing nervous system. Oncogene. 1996 Jan 4;12(1):207–211. [PubMed] [Google Scholar]
  • Luna L, Johnsen O, Skartlien AH, Pedeutour F, Turc-Carel C, Prydz H, Kolstø AB. Molecular cloning of a putative novel human bZIP transcription factor on chromosome 17q22. Genomics. 1994 Aug;22(3):553–562. [PubMed] [Google Scholar]
  • Marks PA, Rifkind RA. Erythroleukemic differentiation. Annu Rev Biochem. 1978;47:419–448. [PubMed] [Google Scholar]
  • Mignotte V, Wall L, deBoer E, Grosveld F, Romeo PH. Two tissue-specific factors bind the erythroid promoter of the human porphobilinogen deaminase gene. Nucleic Acids Res. 1989 Jan 11;17(1):37–54. [PMC free article] [PubMed] [Google Scholar]
  • Mohler J, Vani K, Leung S, Epstein A. Segmentally restricted, cephalic expression of a leucine zipper gene during Drosophila embryogenesis. Mech Dev. 1991 Mar;34(1):3–9. [PubMed] [Google Scholar]
  • Moi P, Chan K, Asunis I, Cao A, Kan YW. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9926–9930. [PMC free article] [PubMed] [Google Scholar]
  • Moi P, Kan YW. Synergistic enhancement of globin gene expression by activator protein-1-like proteins. Proc Natl Acad Sci U S A. 1990 Nov;87(22):9000–9004. [PMC free article] [PubMed] [Google Scholar]
  • Moscovici C, Moscovici MG, Jimenez H, Lai MM, Hayman MJ, Vogt PK. Continuous tissue culture cell lines derived from chemically induced tumors of Japanese quail. Cell. 1977 May;11(1):95–103. [PubMed] [Google Scholar]
  • Motohashi H, Igarashi K, Onodera K, Takahashi S, Ohtani H, Nakafuku M, Nishizawa M, Engel JD, Yamamoto M. Mesodermal- vs. neuronal-specific expression of MafK is elicited by different promoters. Genes Cells. 1996 Feb;1(2):223–238. [PubMed] [Google Scholar]
  • Ney PA, Andrews NC, Jane SM, Safer B, Purucker ME, Weremowicz S, Morton CC, Goff SC, Orkin SH, Nienhuis AW. Purification of the human NF-E2 complex: cDNA cloning of the hematopoietic cell-specific subunit and evidence for an associated partner. Mol Cell Biol. 1993 Sep;13(9):5604–5612. [PMC free article] [PubMed] [Google Scholar]
  • Ney PA, Sorrentino BP, McDonagh KT, Nienhuis AW. Tandem AP-1-binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells. Genes Dev. 1990 Jun;4(6):993–1006. [PubMed] [Google Scholar]
  • Ney PA, Sorrentino BP, Lowrey CH, Nienhuis AW. Inducibility of the HS II enhancer depends on binding of an erythroid specific nuclear protein. Nucleic Acids Res. 1990 Oct 25;18(20):6011–6017. [PMC free article] [PubMed] [Google Scholar]
  • Numoto M, Niwa O, Kaplan J, Wong KK, Merrell K, Kamiya K, Yanagihara K, Calame K. Transcriptional repressor ZF5 identifies a new conserved domain in zinc finger proteins. Nucleic Acids Res. 1993 Aug 11;21(16):3767–3775. [PMC free article] [PubMed] [Google Scholar]
  • Palacios R, Steinmetz M. Il-3-dependent mouse clones that express B-220 surface antigen, contain Ig genes in germ-line configuration, and generate B lymphocytes in vivo. Cell. 1985 Jul;41(3):727–734. [PubMed] [Google Scholar]
  • Rehemtulla A, Warwar R, Kumar R, Ji X, Zack DJ, Swaroop A. The basic motif-leucine zipper transcription factor Nrl can positively regulate rhodopsin gene expression. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):191–195. [PMC free article] [PubMed] [Google Scholar]
  • Shivdasani RA, Rosenblatt MF, Zucker-Franklin D, Jackson CW, Hunt P, Saris CJ, Orkin SH. Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development. Cell. 1995 Jun 2;81(5):695–704. [PubMed] [Google Scholar]
  • Singer D, Cooper M, Maniatis GM, Marks PA, Rifkind RA. Erythropoietic differentiation in colonies of cells transformed by Friend virus. Proc Natl Acad Sci U S A. 1974 Jul;71(7):2668–2670. [PMC free article] [PubMed] [Google Scholar]
  • Soeller WC, Oh CE, Kornberg TB. Isolation of cDNAs encoding the Drosophila GAGA transcription factor. Mol Cell Biol. 1993 Dec;13(12):7961–7970. [PMC free article] [PubMed] [Google Scholar]
  • Stamatoyannopoulos JA, Goodwin A, Joyce T, Lowrey CH. NF-E2 and GATA binding motifs are required for the formation of DNase I hypersensitive site 4 of the human beta-globin locus control region. EMBO J. 1995 Jan 3;14(1):106–116. [PMC free article] [PubMed] [Google Scholar]
  • Sugawara M, Scholl T, Ponath PD, Strominger JL. A factor that regulates the class II major histocompatibility complex gene DPA is a member of a subfamily of zinc finger proteins that includes a Drosophila developmental control protein. Mol Cell Biol. 1994 Dec;14(12):8438–8450. [PMC free article] [PubMed] [Google Scholar]
  • Tsukiyama T, Becker PB, Wu C. ATP-dependent nucleosome disruption at a heat-shock promoter mediated by binding of GAGA transcription factor. Nature. 1994 Feb 10;367(6463):525–532. [PubMed] [Google Scholar]
  • Tsukiyama T, Wu C. Purification and properties of an ATP-dependent nucleosome remodeling factor. Cell. 1995 Dec 15;83(6):1011–1020. [PubMed] [Google Scholar]
  • Tuan D, Solomon W, Li Q, London IM. The "beta-like-globin" gene domain in human erythroid cells. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6384–6388. [PMC free article] [PubMed] [Google Scholar]
  • Tuan DY, Solomon WB, London IM, Lee DP. An erythroid-specific, developmental-stage-independent enhancer far upstream of the human "beta-like globin" genes. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2554–2558. [PMC free article] [PubMed] [Google Scholar]
  • Weber U, Siegel V, Mlodzik M. pipsqueak encodes a novel nuclear protein required downstream of seven-up for the development of photoreceptors R3 and R4. EMBO J. 1995 Dec 15;14(24):6247–6257. [PMC free article] [PubMed] [Google Scholar]
  • Xie T, Belinsky M, Xu Y, Jaiswal AK. ARE- and TRE-mediated regulation of gene expression. Response to xenobiotics and antioxidants. J Biol Chem. 1995 Mar 24;270(12):6894–6900. [PubMed] [Google Scholar]
  • Xiong WC, Montell C. tramtrack is a transcriptional repressor required for cell fate determination in the Drosophila eye. Genes Dev. 1993 Jun;7(6):1085–1096. [PubMed] [Google Scholar]
  • Xue F, Cooley L. kelch encodes a component of intercellular bridges in Drosophila egg chambers. Cell. 1993 Mar 12;72(5):681–693. [PubMed] [Google Scholar]
  • Ye BH, Lista F, Lo Coco F, Knowles DM, Offit K, Chaganti RS, Dalla-Favera R. Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma. Science. 1993 Oct 29;262(5134):747–750. [PubMed] [Google Scholar]
  • Zollman S, Godt D, Privé GG, Couderc JL, Laski FA. The BTB domain, found primarily in zinc finger proteins, defines an evolutionarily conserved family that includes several developmentally regulated genes in Drosophila. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10717–10721. [PMC free article] [PubMed] [Google Scholar]
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