The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence.

Karim, Felix D.; Urness, Lisa D.; Thummel, Carl S.; Klemsz, Michael J.; McKercher, Scott R.; Celada, Antonio; Beveren, Charles Van; Maki, Richard A.; Gunther, Cathy V.; Nye, Julie A.

doi:10.1101/gad.4.9.1451

Cited by 479 publications

(274 citation statements)

References 22 publications

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“…This motif is necessary for the speci®c recognition of a purine-rich core sequence GGAA/T¯anked by more variable but not random 5' and 3' sequences (Karim et al, 1990;Wang et al, 1992). This domain has been shown through deletion analyses to be principally responsible for the sequence-speci®c DNA-binding activities of Ets proteins, although other domains located in the Nor C-terminal part of the protein may regulate the accessibility of the ETS domain to DNA.…”

Section: Introductionmentioning

confidence: 99%

Molecular phylogeny of the ETS gene family

et al. 1999

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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.

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Section: Introductionmentioning

confidence: 99%

Molecular phylogeny of the ETS gene family

et al. 1999

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“…The ETS family of transcription factors share a highly conserved DNA binding domain, termed the`ETS domain', ®rst identi®ed in the gag-myb-ets fusion protein of avian leukemia virus E26 (Nunn et al, 1983;Watson et al, 1988;Karim et al, 1990;Gutman and Wasylyk, 1991;Seth et al, 1992). The ETS domain recognizes and binds to purine rich GGA(A/T) core motifs in the promoters and enhancers of various target genes (Macleod et al, 1992;Wasylyk et al, 1993;Janknecht and Nordheim, 1993;Werner et al, 1995;Kodandapani et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13–15, a region subject to LOH and rearrangement in human carcinoma cell lines

Zhou

Tymms

et al. 1998

Oncogene

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The ETS transcription factors are a large family implicated in the control of cellular proliferation and tumorigenesis. In addition, chromosomal translocations involving ETS family members are associated with a range of di erent human cancers. Given the extensive involvement of ETS factors in tumorigenesis, it becomes important to identify any additional ETS genes that may also play oncogenic roles. We identify a novel gene, ELF5, that appears to belong to the ELF (E74-likefactor) subfamily of the ETS transcription factor family, based upon similarity within the`ETS domain'. ELF5 displays a similar, but more restricted, expression pattern to that of the newly isolated epithelium-speci®c ETS gene, ELF3. Unlike most other ETS family members, ELF5 is not expressed in hematopoietic compartments, but is restricted to organs such as lung, stomach, kidney, prostate, bladder and mammary gland. ELF5 is localized to human chromosome 11p13 ± 15, a region that frequently undergoes loss of heterozygosity (LOH) in several types of carcinoma, including those of breast, kidney and prostate. We ®nd that ELF5 expression is not detectable in a number of carcinoma cell lines, some of which display loss or rearrangement of an ELF5 allele. Similar to other ETS family members, ELF5 displays speci®c binding to DNA sequences containing a GGAA-core. In addition, ELF5 is able to transactivate through these ETS sequences, present upstream from a minimal promoter. Our data suggest that ELF5 may play roles in mammary, lung, prostate and/or kidney function, and possibly also in tumorigenesis.

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“…The c-fos gene promoter contains a serum response element (SRE) that binds a ternary complex containing the serum response factor (SRF), Elk-1, and SRF Accessory Proteins (SAP)-1 and -2 (Norman et al, 1988;Price et al, 1995). Adjacent to the SRE is an ETS motif which is necessary for DNA-binding by the ternary complex (Karim et al, 1990). Adjoining the SRE is an AP-1 site (TRE), which appears to be constitutively occupied in vivo (Herrera et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Suppression of c-Fos gene transcription with malignant transformation of human bronchial epithelial cells

et al. 1998

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The Activator Protein-1 (AP-1) complex is a dimeric transcription factor composed of fos and jun proteins that regulates cellular growth and di erentiation. We previously demonstrated a reduction in basal AP-1 transcriptional activity associated with the malignant transformation of human bronchial epithelial (HBE) cells that was, in part, a consequence of decreased c-fos expression. In this study, we investigated the mechanisms underlying the reduction in c-fos expression associated with the malignant transformation of HBE cells. c-Fos gene transcription was lower in tumorigenic HBE cells than in normal HBE cells, and the reduction in transcription involved c-fos gene promoter elements from 7327 to +40. DNaseI footprinting and band shift analyses of motifs within this c-fos promoter region, including a cyclic AMP response element (CRE), serum response element (SRE), sis-inducible element (SIE), and a YY1 site, revealed that binding to these motifs was greater in tumorigenic HBE cells than in normal HBE cells. Site-directed mutagenesis of the CRE partially relieved the repression of c-fos promoter activity in tumorigenic HBE cells. Further, the activity of the Jun N-terminal Kinase (JNK)-dependent pathway, which was a positive regulator of the c-fos promoter, was greater in normal HBE cells than in tumorigenic HBE cells. These ®ndings demonstrate a transcriptionally-mediated suppression of c-fos gene expression associated with the malignant transformation of HBE cells. The decreased activity of the c-fos promoter in tumorigenic 1170I cells appeared to involve suppression through a CRE site and reduced activation by JNK-dependent pathways.

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The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence.

Cited by 479 publications

References 22 publications

Molecular phylogeny of the ETS gene family

Molecular phylogeny of the ETS gene family

A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13–15, a region subject to LOH and rearrangement in human carcinoma cell lines

Suppression of c-Fos gene transcription with malignant transformation of human bronchial epithelial cells

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