The ets genes family encodes a group of proteins which function as transcription factors under physiological conditions. We report here that the Erg proteins, members of the Ets family, form homo and heterodimeric complexes in vitro. We demonstrate that the Ergp55 protein isoform forms dimers with itself and with the two other isoforms, Ergp49 and Ergp38. Using a set of Erg protein deletion mutants, we de®ne two distinct domains independently involved in dimerization. The ®rst one is located in the amino-terminal part of the protein containing the pointed domain (PNT), conserved in a subset of Ets proteins. The second one resides within the ETS domain, the DNA-binding domain. We also show that the Erg protein central region behaves as an inhibitory domain of dimerization and its removal enhances the Ergp55 transactivation properties. Furthermore, Ergp55 forms heterodimers with some other Ets proteins. Among the latter, we show that Fli-1, Ets-2, Er81 and Pu-1 physically interact with Erg. Finally, we show that the formation of the previously described ternary complex Ergp55/Fos/jun is mediated by ETS domain and Jun protein, while the ternary complex Ergp49/Fos/Jun is mediated by Fos protein.

FLI-1 is an ETS family transcription factor which is overexpressed in

We have constructed a molecular phylogeny of the ETS gene family. By distance and parsimony analysis of the ETS conserved domains we show that the family containing so far 29 di erent genes in vertebrates can be divided into 13 groups of genes namely ETS, ER71, GABP, PEA3, ERG, ERF, ELK, DETS4, ELF, ESE, TEL, YAN, SPI. Since the three dimensional structure of the ETS domain has revealed a similarity with the winged-helix ± turn ± helix proteins, we used two of them (CAP and HSF) to root the tree. This allowed us to show that the family can be divided into ®ve subfamilies: ETS, DETS4, ELF, TEL and SPI. The ETS subfamily comprises the ETS, ER71, GABP, PEA3, ERG, ERF and the ELK groups which appear more related to each other than to any other ETS family members. The fact that some members of these subfamilies were identi®ed in early metazoans such as diploblasts and sponges suggests that the diversi®cation of ETS family genes predates the diversi®cation of metazoans. By the combined analysis of both the ETS and the PNT domains, which are conserved in some members of the family, we showed that the GABP group, and not the ERG group, is the one most closely related to the ETS group. We also observed that the speed of accumulation of mutations in the various genes of the family is highly variable. Noticeably, paralogous members of the ELK group exhibit strikingly di erent evolutionary speed suggesting that the evolutionary pressure they support is very di erent.

Ets proteins are a family of transcription factors that regulate the expression of a myriad of genes in a variety of tissues and cell types. This functional versatility emerges from their interactions with other structurally unrelated transcription factors. Indeed, combinatorial control is a characteristic property of Ets family members, involving interactions between Ets and other key transcriptional factors such as AP1, SRF, and Pax family members. Intriguingly, recent molecular modeling and crystallographic data suggest that not only the ETS DNA-binding domain, but also the DNA recognition helix alpha3, are often directly required for Ets partner's selection. Indeed, while most DNA-binding proteins appear to exploit differences within their DNA recognition helices for sites selection, the Ets proteins exploit differences in their surfaces that interact with other transcription factors, which in turn may modify their DNA-binding properties in a promoter-specific fashion. Taken together, the gene-specific architecture of these unique complexes can mediate the selective control of transcriptional activity.

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The results indicate that the promoter activity of the 760/+19 region of the vWF gene depends on transcription factors of the Ets family of which several members like Ets-1, Ets-2 and Erg are expressed in endothelium. Cotransfection of Ets-1 and Erg expression plasmids is su cient to induce the 760/+19 vWF promoter activity in HeLa cells.

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Highly glycosylated regions or glycopeptides were obtained by proteolysis of human tracheobronchial mucins. They were chemically deglycosylated and the resulting products were used to raise a rabbit antiserum. This antiserum specifically recognized the superanuclear region of respiratory and colonic goblet cells as areas around and below the nucleus of mucin-secreting cells in tracheobronchial mucous glands. A lambda gt11 cDNA library constructed from human tracheobronchial mucosa was screened with this antiserum. Ten positive clones were obtained from screening half of the library (about 10(6) recombinants). The antibodies were purified by absorption to each positive clone; some purified antibodies were specific for goblet cells and others recognized both goblet and mucous cells, indicating that there is differential cellular expression of mucin peptides. The total or partial amino acid sequences deduced from these cDNA clones could be classified into three groups. The first group contained repetitive sequences of eight amino acid residues, almost perfectly identical, and in different arrangements. The second type exhibited homology at their amino and carboxy-terminal ends. The last group had no distinctive feature except for a high content of hydroxy amino acids typical of mucins. Five different clones could correspond to the carboxy-terminal end of tracheobronchial apomucins. These results indicate that human tracheobronchial apomucins consist of a family of different proteins.