Direct role for Myc in transcription initiation mediated by interactions with TFII-I

Roy, Ananda L.; Carruthers, Christopher; Gutjahr, Thomas; Roeder, Robert G.

doi:10.1038/365359a0

Cited by 244 publications

(186 citation statements)

References 27 publications

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“…No consensus TATA box was present, although two AT-rich TATA-like sequences were found. Other potentially important transcription-factor-binding sites were found including those that many play a role in cell proliferation and differentiation (c-myc, c-myb) [28,29], gene induction 838 l Tissue-specific regulation of human dipeptidyl peptidase IV gene promoter [ …”

Section: Resultsmentioning

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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Section: Resultsmentioning

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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“…Sequence analysis of the gadd45 promoter revealed that this regulatory region lacks canonical Myc binding sites; a characteristic which is common among genes which are repressed by Myc (Antonson et al, 1995;Facchini et al, 1997). Recent studies suggest that Myc may repress gene expression either by directly interacting with components of the basal transcription machinery or by inhibiting transcription through an initiator element (Li et al, 1994;Philipp et al, 1994;Roy et al, 1993). Interestingly, the gadd45 gene lacks both an initiator site and a TATA box.…”

Section: Discussionmentioning

confidence: 99%

Myc represses the growth arrest gene gadd45

et al. 1997

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The c-Myc protein strongly stimulates cellular proliferation, inducing cells to exit G0/G1 and enter the cell cycle. At a molecular level, Myc prevents growth arrest and drives cell cycle progression through the transcriptional regulation of Myc-target genes. Expression of the growth arrest and DNA damage inducible gene 45 (gadd45) is elevated in response to DNA damaging agents, such as ionizing radiation via a p53-dependent mechanism, upon nutrient deprivation, or during di erentiation. Gadd45 holds a vital role in growth arrest as ectopic expression confers a strong block to proliferation. Exposure of quiescent cells to mitogen stimulates a rapid increase in c-Myc expression which is followed by the subsequent reduction in gadd45 expression. The kinetics of these two regulatory events suggest that Myc suppresses the expression of gadd45, contributing to G0/ G1 phase exit of the cell cycle. Indeed, ectopic Myc expression in primary and immortalized ®broblasts results in the suppression of gadd45 mRNA levels, by a mechanism which is independent of cell cycle progression. Using an inducible MycER TM system, rapid suppression of gadd45 mRNA is ®rst evident approximately 0.5 h following Myc activation. The reduction in gadd45 mRNA expression occurs at the transcriptional level and is mediated by a p53-independent pathway. Moreover, Myc suppression and p53 induction of gadd45 following exposure to ionizing radiation are noncompetitive co-regulatory events. Myc suppression of gadd45 de®nes a novel pathway through which Myc promotes cell cycle entry and prevents growth arrest of transformed cells.

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“…(e) Parental 3T3 cells and the myc transfectants were treated with or without FR901228 at 10 ng/ml for 24 h. The expression of FasL detected by RT ± PCR followed by Southern blotting analysis. The expression of b-actin was used as a control growth and di erentiation (Green and Scott, 1994;Roy et al, 1993). It is conceivable that c-Myc is in¯uencing the transcription of genes critical to the initiation of apoptosis (Mercep et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Fungal metabolite FR901228 inhibits c-Myc and Fas ligand expression

et al. 1998

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Activation of T lymphocytes often leads to cellular activation, production of cytokines, entry into cell cycle, and expression of Fas (CD95) and Fas ligand (FasL). Although it is well established that the interaction of Fas and FasL results in apoptosis, mechanisms for regulated expression of Fas and FasL are unclear. Our previous work with antisense oligodeoxynucleotides suggested that the protooncogene c-myc is obligatory for activationinduced apoptosis. To study the relationship between cmyc and the Fas/FasL expression, we employed the antisense method and a newly identi®ed fungal metabolite, FR901228, which has been shown to speci®cally inhibit expression of c-myc in ®broblasts. We found that FR901228 could e ectively block activation-induced apoptosis in T cell hybridomas and this was correlated with its speci®c inhibition of c-myc expression. Both FR901228 and antisense oligodeoxynucleotide to c-myc had similar e ect in inhibiting FasL expression. These treatments did not a ect activation-induced production of IL-2, nor the expression of Fas. In addition, FR901228 inhibited the expression of FasL in 3T3 ®broblasts, but not these transfected with c-myc, supporting a speci®c role of c-myc in this process. Thus, c-Myc plays a fundamental role in the regulation of the expression of FasL, but not Fas and IL-2. Our data further de®ned the requirement of c-Myc in activation-induced apoptosis in T cells.

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Direct role for Myc in transcription initiation mediated by interactions with TFII-I

Cited by 244 publications

References 27 publications

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

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

Myc represses the growth arrest gene gadd45

Fungal metabolite FR901228 inhibits c-Myc and Fas ligand expression

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