A position- and orientation-dependent element in the first intron is required for expression of the mouse hprt gene in embryonic stem cells

Magin, Thomas M.; McEwan, Carolanne; Milne, Marion; Pow, Angela M.; Selfridge, Jim; Melton, David W.

doi:10.1016/0378-1119(92)90217-d

Cited by 21 publications

(9 citation statements)

References 33 publications

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“…Placing the UbC intron, alone or with the flanking exon 1, upstream of the proximal promoter, in both sense and antisense orientation, caused a drastic drop of luciferase expression, demonstrating that the intron was not able to support expression when localized outside the transcribed region, even if the other promoter elements were present. This evidence suggests that the UbC intron is not acting as a typical transcriptional enhancer, but rather regulates gene expression in a context-dependent manner, as reported for other intronic cis -elements which affect promoter activity orientation- or orientation- and position-dependently [45], [46].…”

Section: Discussionsupporting

confidence: 58%

Yin Yang 1 Intronic Binding Sequences and Splicing Elicit Intron-Mediated Enhancement of Ubiquitin C Gene Expression

et al. 2013

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In a number of organisms, introns affect expression of the gene in which they are contained. Our previous studies revealed that the 5′-UTR intron of human ubiquitin C (UbC) gene is responsible for the boost of reporter gene expression and is able to bind, in vitro, Yin Yang 1 (YY1) trans-acting factor. In this work, we demonstrate that intact YY1 binding sequences are required for maximal promoter activity and YY1 silencing causes downregulation of luciferase mRNA levels. However, YY1 motifs fail to enhance gene expression when the intron is moved upstream of the proximal promoter, excluding the typical enhancer hypothesis and supporting a context-dependent action, like intron-mediated enhancement (IME). Yet, almost no expression is seen in the construct containing an unspliceable version of UbC intron, indicating that splicing is essential for promoter activity. Moreover, mutagenesis of YY1 binding sites and YY1 knockdown negatively affect UbC intron removal from both endogenous and reporter transcripts. Modulation of splicing efficiency by YY1 cis-elements and protein factor may thus be part of the mechanism(s) by which YY1 controls UbC promoter activity. Our data highlight the first evidence of the involvement of a sequence-specific DNA binding factor in IME.

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Section: Discussionsupporting

confidence: 58%

Yin Yang 1 Intronic Binding Sequences and Splicing Elicit Intron-Mediated Enhancement of Ubiquitin C Gene Expression

et al. 2013

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“…Because the predominant retarded band of gel‐mobility shift experiments was obtained using the intronic probe P2 containing one putative octamer‐binding site and EcRE half‐site, the short intron 1, characteristic of cuticular protein genes, could be considered as an important element in the transcriptional regulation of ACP‐20 . Increasing numbers of studies emphasize the importance of regulatory elements located within introns, and most often in intron 1, of housekeeping as well as tissue‐specifically expressed genes, and such sequences are characterized as positive or negative regulatory elements, enhancers or silencers and as alternative intronic promoters (reviewed in Magin et al ., 1992; Fatyol et al ., 1999; Wang et al ., 2002; Kolb, 2003). It has also been reported that the mere presence of an intron can increase gene expression levels and that an exogenous intron could be recognized by the splicing machinery, leading to an increase in transgene expression levels (Palmiter et al ., 1991; Choi et al ., 1991; Duncker et al ., 1997).…”

Section: Discussionmentioning

confidence: 99%

A functional analysis of ACP‐20, an adult‐specific cuticular protein gene from the beetle Tenebrio: role of an intronic sequence in transcriptional activation during the late metamorphic period

Lemoine¹,

Mathelin²,

Braquart‐Varnier³

et al. 2004

Insect Molecular Biology

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A gene encoding the adult cuticular protein ACP-20 was isolated in Tenebrio. It consists of three exons interspersed by two introns, intron 1 interrupting the signal peptide. To understand the regulatory mechanisms of ACP-20 expression, ACP-20 promoter-luciferase reporter gene constructs were transfected into cultured pharate adult wing epidermis. Transfection assays needed the presence of 20-hydroxyecdysone, confirming that ACP-20 is up-regulated by ecdysteroids. Analysis of 5' deletion constructs revealed that three regions are necessary for high levels of transcription. Interaction experiments between intronic fragments and epidermal nuclear proteins confirmed the importance of intron 1 in ACP-20 transcriptional control, which results from the combined activity of regulatory cis-acting elements of the promoter and those of intron 1.

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“…Classically, cis-enhanding elements have been reported to up-regulate the homologous promoter in an orientation-and positionindependent manner. However, recently, some intronic enhancers have been reported to up-regulate the homologous and/or heterologous promoter orientationdependently [41,42], or orientation-and positiondependently [43]. We assume that the CAGCTG motif in intron 1 also regulates the gene expression in a contextdependent manner.…”

Section: Discussionmentioning

confidence: 99%

A complex composed of USF1 and USF2 activates the human FcεRI α chain expression via a CAGCTG element in the first intron

Takahashi

Nishiyama

et al. 2001

Eur. J. Immunol.

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A position- and orientation-dependent element in the first intron is required for expression of the mouse hprt gene in embryonic stem cells

Cited by 21 publications

References 33 publications

Yin Yang 1 Intronic Binding Sequences and Splicing Elicit Intron-Mediated Enhancement of Ubiquitin C Gene Expression

Yin Yang 1 Intronic Binding Sequences and Splicing Elicit Intron-Mediated Enhancement of Ubiquitin C Gene Expression

A functional analysis of ACP‐20, an adult‐specific cuticular protein gene from the beetle Tenebrio: role of an intronic sequence in transcriptional activation during the late metamorphic period

A complex composed of USF1 and USF2 activates the human FcεRI α chain expression via a CAGCTG element in the first intron

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