Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins

TRANSCRIPTION factor NF-E2 is crucial for regulating erythroid-specific gene expression1. Cloning of the NF-E2 p45 protein has revealed that it contains a basic region–leucine zipper (b-zip) domain which associates with another unidentified protein (of relative molecular mass 18,000) to form functional NF-E2 (ref. 2). We show here that products of the maf proto-oncogene family3–5, MafF, MafG and MafK (the small Maf proteins) which possess a b-zip DNA-binding domain but lack a canonical transactivation domain3, directly control the DNA-binding properties of p45 by heterodimeric association with p45. Whereas homodimers of the small Maf proteins act as negative regulators, heterodimers composed of Maf and p45 support active transcription in vivo. These results indicate that one (or all) of the small Maf proteins is the second constituent chain required for NF-E2 activity, and that negative as well as positive regulation can be achieved through an NF-E2 site, depending on the equilibrium concentrations of p45 and the Maf proteins inside erythroid cells.

[1]  K. Kataoka,et al.  v-maf, a viral oncogene that encodes a "leucine zipper" motif. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[2]  S. Nagata,et al.  pEF-BOS, a powerful mammalian expression vector. , 1990, Nucleic acids research.

[3]  K. Kataoka,et al.  Structure-function analysis of the maf oncogene product, a member of the b-Zip protein family , 1993, Journal of virology.

[4]  W. Schaffner,et al.  A cloned octamer transcription factor stimulates transcription from lymphoid–specific promoters in non–B cells , 1988, Nature.

[5]  H. Zentgraf,et al.  Hormone-dependent terminal differentiation in vitro of chicken erythroleukemia cells transformed by ts mutants of avian erythroblastosis virus , 1982, Cell.

[6]  S. Sassa,et al.  Erythroleukemia differentiation. Distinctive responses of the erythroid-specific and the nonspecific delta-aminolevulinate synthase mRNA. , 1991, The Journal of biological chemistry.

[7]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[8]  T. Ley,et al.  Conservation of the primary structure, organization, and function of the human and mouse beta-globin locus-activating regions. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. D. Engel,et al.  Activity and tissue-specific expression of the transcription factor NF-E1 multigene family. , 1990, Genes & development.

[10]  K. Kataoka,et al.  Maf nuclear oncoprotein recognizes sequences related to an AP-1 site and forms heterodimers with both Fos and Jun , 1994, Molecular and cellular biology.

[11]  K. Kataoka,et al.  Two new members of the maf oncogene family, mafK and mafF, encode nuclear b-Zip proteins lacking putative trans-activator domain. , 1993, Oncogene.

[12]  T. Kouzarides,et al.  Leucine zippers of fos, jun and GCN4 dictate dimerization specificity and thereby control DNA binding , 1989, Nature.

[13]  M. Reitman,et al.  Mutational analysis of the chicken beta-globin enhancer reveals two positive-acting domains. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[14]  T. Cox,et al.  Human erythroid 5‐aminolevulinate synthase: promoter analysis and identification of an iron‐responsive element in the mRNA. , 1991, The EMBO journal.

[15]  S. Orkin.  Globin gene regulation and switching: Circa 1990 , 1990, Cell.

[16]  C. Vinson,et al.  Dimerization specificity of the leucine zipper-containing bZIP motif on DNA binding: prediction and rational design. , 1993, Genes & development.

[17]  Paul Tempst,et al.  Erythroid transcription factor NF-E2 is a haematopoietic-specific basic–leucine zipper protein , 1993, Nature.

[18]  P S Kim,et al.  Preferential heterodimer formation by isolated leucine zippers from fos and jun. , 1989, Science.

[19]  P. Romeo,et al.  Cis- and trans-acting elements involved in the regulation of the erythroid promoter of the human porphobilinogen deaminase gene. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[20]  M. Lai,et al.  Continuous tissue culture cell lines derived from chemically induced tumors of Japanese quail , 1977, Cell.

[21]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.