Promoter Sequences of Eukaryotic Protein-Coding Genes

Corden, Jeffry L.; Wasylyk, Bohdan; Buchwalder, Anne; Sassone–Corsi, Paolo; Kédinger, Claude; Chambon, Pierre

doi:10.1126/science.6251548

Cited by 965 publications

(449 citation statements)

References 37 publications

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“…This transcript initiation site was found in RACE cDNA clones from the CFPAC-1 pancreas adenocarcinoma cell line, the ZR75-1 breast carcinoma cell line, and from normal pancreas. The sequence after the ®rst nucleotide is in good agreement with the consensus sequence of a transcript initiation site ([A/G]YYYYY) (Corden et al, 1980). Finally, the length of the consensus sequence (1584 nucleotides) is su cient to account for the 1.8 ± 2.0 kb mRNA seen on Northern blots when polyadenylation is taken into account.…”

Section: Identi®cation and Cloning Of Cbl-3supporting

confidence: 58%

cbl-3: a new mammalian cbl family protein

et al. 1999

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We have cloned a new human gene, cbl-3, which encodes a protein with marked homology to the cbl family of proteins. The predicted protein encoded by this gene retains the conserved phosphotyrosine binding domain (PTB) in the N-terminal and the zinc ®nger but is signi®cantly shorter (MW 52.5 kDa) than the other mammalian cbl proteins. The protein lacks the extensive proline rich domain and leucine zipper seen in c-cbl and cbl-b and structurally most resembles the C. elegans and Drosophila cbl proteins. The gene is ubiquitously expressed with highest expression in the aerodigestive tract, prostate, adrenal gland, and salivary gland. The protein is phosphorylated and recruited to the EGFR upon EGF stimulation and inhibits EGF stimulated MAP kinase activation. In comparison to the other mammalian cbl proteins (e.g. cbl-b), cbl-3 interacts with a restricted range of proteins containing Src Homology 3 regions. An alternatively spliced form of the cbl-3 protein was also identi®ed which deletes a critical region of the PTB domain and which does not interact with the EGFR nor inhibit EGF stimulated MAP kinase activation. These data demonstrate that cbl-3, a novel mammalian cbl protein, is a regulator of EGFR mediated signal transduction.

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Section: Identi®cation and Cloning Of Cbl-3supporting

confidence: 58%

cbl-3: a new mammalian cbl family protein

et al. 1999

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“…Still, the absence of a strong TATA box may lead to a large number of transcription initiation sites seen in Figure 3. Other promoters without consensus TATA boxes also exhibit multiple start sites [43][44][45].…”

Section: Identification Of Transcriptional Start Sitesmentioning

confidence: 99%

Human dipeptidyl peptidase IV gene promoter: tissue-specific regulation from a TATA-less GC-rich sequence characteristic of a housekeeping gene promoter

Böhm

Gum

Erickson

et al. 1995

Biochemical Journal

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The dipeptidyl peptidase IV gene encodes a plasma-membrane exopeptidase that is highly expressed in small intestine, lung and kidney. In order to better understand the mechanisms responsible for this tissue-specific expression we cloned, sequenced and functionally characterized the 5′-flanking region of the human dipeptidyl peptidase IV gene. The first 500 bases of the 5′-flanking sequence constituted an unmethylated CpG island, contained several Sp1-binding sites and lacked a consensus TATA box, all characteristics of gene promoters lacking tissue-specific expression. RNase-protection analysis using both small intestinal and Caco2 cell RNA indicated that the dipeptidyl peptidase IV transcript was initiated from no fewer than six major and 12 minor start sites. The 5′-flanking sequence also exhibited functional promoter activity in transient transfection experiments. Here, various lengths of the sequence were cloned upstream of a luciferase gene and introduced into cultured cells using lipofectin. A region located between bases -150 and -109 relative to the start of translation was found to be important for high-level promoter activity in both Caco2 and HepG2 cells. Moreover, Caco2 cells and HepG2 cells, which express high levels of dipeptidyl peptidase IV activity, exhibited much higher normalized luciferase activity after transfection than did 3T3, Jurkat or COS-7 cells, which have low enzyme levels. Sodium butyrate was found to increase both enzyme activity and normalized luciferase in HepG2 cells. Thus the dipeptidyl peptidase IV promoter possesses the ability to initiate transcription in a tissue-specific fashion in spite of having the sequence characteristics of a housekeeping gene promoter.

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“…[39][40][41][42][43][44] This may also explain, why the deletion of the TATA-consensus sequence as shown in Figure 1b was associated only with a reduction but not complete loss of IL-10 promoter activity in BL cells. There exists a potential initiation site ͗ACAT͘ at −27 which is similar to a YY1 core binding sequence and could be the place for binding of the RNA-polymerase II complex to direct the expression of IL-10 in EBV-positive B cells.…”

Section: Discussionmentioning

confidence: 99%

The AT-rich region between −54 to −66 is important for the promoter activity of interleukin-10 in Epstein–Barr virus positive Burkitt’s lymphoma cells

et al. 1999

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IL-10 is an important regulatory cytokine. The recent characterization of the 5Ј-flanking region of IL-10 led to the identification of the promoter region. The infection of B cells with EBV induces IL-10 production which may contribute to EBV-induced transformation. In the present report, IL-10 promoter elements involved in the constitutive expression of IL-10 in EBV-positive lymphoma cells are described. The AT-rich region between −54/−66 from the transcriptional start site was found to be important for IL-10-promoter activity in BL36. A point mutation at position −60 (T/A) was associated with over 90% reduction of luciferase activity in the cell lines BL36 and BL74. The conversion of A/T at position −57 led to enhanced promoter activity. In addition the AT-rich region could serve as an enhancer for the ␤-globin basic promoter. In BJAB cells (EBV-negative), sequences between −205/−139 rather than the AT-rich region were involved in IL-10 promoter regulation. This underlines the importance of the AT-rich region for EBV-associated IL-10 promoter regulation. Our results further the understanding of how the IL-10 gene could be regulated in B cell lymphomas.

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Promoter Sequences of Eukaryotic Protein-Coding Genes

Cited by 965 publications

References 37 publications

cbl-3: a new mammalian cbl family protein

cbl-3: a new mammalian cbl family protein

Human dipeptidyl peptidase IV gene promoter: tissue-specific regulation from a TATA-less GC-rich sequence characteristic of a housekeeping gene promoter

The AT-rich region between −54 to −66 is important for the promoter activity of interleukin-10 in Epstein–Barr virus positive Burkitt’s lymphoma cells

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