Nobel Lecture: Prions

CpG islands in vertebrate genomes.

A 30-amino-acid segment of C/EBP, a newly discovered enhancer binding protein, shares notable sequence similarity with a segment of the cellular Myc transforming protein. Display of these respective amino acid sequences on an idealized alpha helix revealed a periodic repetition of leucine residues at every seventh position over a distance covering eight helical turns. The periodic array of at least four leucines was also noted in the sequences of the Fos and Jun transforming proteins, as well as that of the yeast gene regulatory protein, GCN4. The polypeptide segments containing these periodic arrays of leucine residues are proposed to exist in an alpha-helical conformation, and the leucine side chains extending from one alpha helix interdigitate with those displayed from a similar alpha helix of a second polypeptide, facilitating dimerization. This hypothetical structure is referred to as the "leucine zipper," and it may represent a characteristic property of a new category of DNA binding proteins.

https://science.sciencemag.org/content/sci/240/4860/1759.full.pdf

The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins

The cloning of genes encoding mammalian DNA binding transcription factors for RNA polymerase II has provided the opportunity to analyze the structure and function of these proteins. This review summarizes recent studies that define structural domains for DNA binding and transcriptional activation functions in sequence-specific transcription factors. The mechanisms by which these factors may activate transcriptional initiation and by which they may be regulated to achieve differential gene expression are also discussed.

https://science.sciencemag.org/content/sci/245/4916/371.full.pdf

Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins

Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor.

Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain.

https://www.cell.com/cell/pdf/0092-8674(83)90210-6.pdf

The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter

The biochemical analysis of cellular trans-activators involved in promoter recognition provides an important step toward understanding the mechanisms of gene expression in animal cells. The promoter selective transcription factor, Sp1, has been purified from human cells to more than 95 percent homogeneity by sequence-specific DNA affinity chromatography. Isolation and renaturation of proteins purified from sodium dodecyl sulfate polyacrylamide gels allowed the identification of two polypeptides (105 and 95 kilodaltons) as those responsible for recognizing and interacting specifically with the GC-box promoter elements characteristic of Sp1 binding sites.

https://science.sciencemag.org/content/sci/234/4772/47.full.pdf

Robert Tjian

Papers

Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain.

The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter

Purification and biochemical characterization of the promoter-specific transcription factor, Sp1

Isolation of transcription factors that discriminate between different promoters recognized by RNA polymerase II

Transcriptional selectivity of viral genes in mammalian cells.