A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins

Two cDNAs were isolated whose dimerized products bind specifically to a DNA sequence, kappa E2, located in the immunoglobulin kappa chain enhancer. Both cDNAs share a region of extensive identity to the Drosophila daughterless gene and obvious similarity to a segment in three myc proteins, MyoD, and members of the Drosophila achaete-scute and twist gene family. The homologous regions have the potential to form two amphipathic helices separated by an intervening loop. Remarkable is the stringent conservation of hydrophobic residues present in both helices. We demonstrate that this new motif plays a crucial role in both dimerization and DNA binding.

[1]  S. McKnight,et al.  The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. , 1988, Science.

[2]  P. Leder,et al.  The human c-myc oncogene: Structural consequences of translocation into the igh locus in Burkitt lymphoma , 1983, Cell.

[3]  K. Moelling,et al.  Nuclear localization and DNA binding of the transforming gene product of avian myelocytomatosis virus , 1982, Nature.

[4]  P. Sharp,et al.  The B-cell-specific Oct-2 protein contains POU box- and homeo box-type domains. , 1988, Genes & development.

[5]  S. Tapscott,et al.  MyoD1: a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts. , 1988, Science.

[6]  M. Kirschner,et al.  Homologies in both primary and secondary structure between nuclear envelope and intermediate filament proteins , 1986, Nature.

[7]  D. Baltimore,et al.  Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility. , 1987, Science.

[8]  P. Sharp,et al.  Cloning of a lymphoid-specific cDNA encoding a protein binding the regulatory octamer DNA motif. , 1988, Science.

[9]  T. Cline,et al.  The Drosophila sex determination gene daughterless has different functions in the germ line versus the soma , 1987, Cell.

[10]  H. Weintraub,et al.  Expression of a single transfected cDNA converts fibroblasts to myoblasts , 1987, Cell.

[11]  G. Evan,et al.  The protein encoded by the human proto-oncogene c-myc. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[12]  P. Leder,et al.  Nuclear localization and DNA binding properties of a protein expressed by human c-myc oncogene. , 1984, Science.

[13]  B. Thisse,et al.  Sequence of the twist gene and nuclear localization of its protein in endomesodermal cells of early Drosophila embryos. , 1988, The EMBO journal.

[14]  G. Rose,et al.  Loops in globular proteins: a novel category of secondary structure. , 1986, Science.

[15]  U. Siebenlist,et al.  The regulation and expression of c-myc in normal and malignant cells. , 1986, Annual review of immunology.

[16]  W. Rutter,et al.  Systematic binding analysis of the insulin gene transcription control region: insulin and immunoglobulin enhancers utilize similar transactivators , 1988, Molecular and cellular biology.

[17]  H. Varmus,et al.  Definition of regions in human c-myc that are involved in transformation and nuclear localization , 1987, Molecular and cellular biology.

[18]  R. Villares,et al.  The achaete-scute gene complex of D. melanogaster: Conserved Domains in a subset of genes required for neurogenesis and their homology to myc , 1987, Cell.

[19]  P. Sharp,et al.  Distinct factors bind to apparently homolgous sequences in the immunoglobulin heavy-chain enhancer , 1986, Nature.

[20]  P. Sharp,et al.  Molecular cloning of an enhancer binding protein:Isolation by screening of an expression library with a recognition site DNA , 1988, Cell.

[21]  K. Danna.  Determination of fragment order through partial digests and multiple enzyme digests. , 1980, Methods in enzymology.

[22]  W. Gilbert,et al.  Sequencing end-labeled DNA with base-specific chemical cleavages. , 1980, Methods in enzymology.

[23]  G. Church,et al.  Cell-type-specific contacts to immunoglobulin enhancers in nuclei , 1985, Nature.

[24]  A. Feinberg,et al.  A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[25]  Y. Jan,et al.  The maternal sex determination gene daughterless has zygotic activity necessary for the formation of peripheral neurons in Drosophila. , 1988, Genes & development.

[26]  T. Cline.  A sex-specific, temperature-sensitive maternal effect of the daughterless mutation of Drosophila melanogaster. , 1976, Genetics.

[27]  G. Church,et al.  B lineage--specific interactions of an immunoglobulin enhancer with cellular factors in vivo. , 1985, Science.

[28]  David Baltimore,et al.  Multiple nuclear factors interact with the immunoglobulin enhancer sequences , 1986, Cell.

[29]  F. Alt,et al.  The human myc gene family. , 1986, Cold Spring Harbor symposia on quantitative biology.

[30]  F. Alt,et al.  The human myc gene family: structure and activity of L-myc and an L-myc pseudogene. , 1987, Genes & development.

[31]  Y. Jan,et al.  daughterless, a Drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex , 1988, Cell.

[32]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[33]  R. Kennett,et al.  Identification and characterization of the NMYC gene product in human neuroblastoma cells by monoclonal antibodies with defined specificities. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[34]  B. S. Baker,et al.  Molecular genetic aspects of sex determination in Drosophila , 1987, BioEssays : news and reviews in molecular, cellular and developmental biology.

[35]  T. Cline,et al.  Molecular characterization of daughterless, a Drosophila sex determination gene with multiple roles in development. , 1988, Genes & development.