Regulation of eukaryotic gene expression by the untranslated gene regions and other non-coding elements

Barrett, Lucy W.; Fletcher, Sue; Wilton, Steve D.

doi:10.1007/s00018-012-0990-9

Cited by 491 publications

(411 citation statements)

References 199 publications

(285 reference statements)

Supporting

Mentioning

399

Contrasting

Unclassified

Order By: Relevance

“…These data also demonstrate, for the first time, that the 5 0 UTRdependent modulation of GLA gene expression may vary among different cell types. The expression of alternative 5 0 UTRs represents an evolutionary gain of transcriptional and translational control pathways, allowing tissue-specific expression patterns and expanding the repertoire of expression from a single gene locus (Barrett et al 2012). Although GLA is a housekeeping gene, aGal activity levels vary greatly from organ to organ and in different cell types (Brady et al 1967;von Scheidt et al 1991).…”

Section: Discussionmentioning

confidence: 99%

The Modulatory Effects of the Polymorphisms in GLA 5′-Untranslated Region Upon Gene Expression Are Cell-Type Specific

2015

View full text Add to dashboard Cite

Lysosomal a-galactosidase A (aGal) is the enzyme deficient in Fabry disease (FD). The 5 0 -untranslated region (5 0 UTR) of the aGal gene (GLA) shows a remarkable degree of variation with three common single nucleotide polymorphisms at nucleotide positions c.-30G>A, c.-12G>A and c.-10C>T. We have recently identified in young Portuguese stroke patients a fourth polymorphism, at c.-44C>T, co-segregating in cis with the c.-12A allele. In vivo, the c.-30A allele is associated with higher enzyme activity in plasma, whereas c.-10T is associated with moderately decreased enzyme activity in leucocytes. Limited data suggest that c.-44T might be associated with increased plasma aGal activity. We have used a luciferase reporter system to experimentally assess the relative modulatory effects on gene expression of the different GLA 5 0 UTR polymorphisms, as compared to the wild-type sequence, in four different human cell lines. Group-wise, the relative luciferase expression patterns of the various GLA variant isoforms differed significantly in all four cell lines, as evaluated by non-parametric statistics, and were cell-type specific. Some of the post hoc pairwise statistical comparisons were also significant, but the observed effects of the GLA 5 0 UTR polymorphisms upon the luciferase transcriptional activity in vitro did not consistently replicate the in vivo observations. These data suggest that the GLA 5 0 UTR polymorphisms are possible modulators of the aGal expression. Further studies are needed to elucidate the biological and clinical implications of these observations, particularly to clarify the effect of these polymorphisms in individuals carrying GLA variants associated with high residual enzyme activity, with no or mild FD clinical phenotypes.

show abstract

Section: Discussionmentioning

confidence: 99%

The Modulatory Effects of the Polymorphisms in GLA 5′-Untranslated Region Upon Gene Expression Are Cell-Type Specific

2015

View full text Add to dashboard Cite

show abstract

“…Recent studies reported a correlation between enhancers and chromatin state, including dependence on histone modifications. Enhancers increase the availability of DNA to replication and transcription factors, as well as intensify these processes (Barrett et al 2012). The effect of interactions between enhancers and promoters depends on the distance between them only if it is as significant as several thousand base pairs and then inhibits the enhancers' activity.…”

Section: Enhancer Sequencesmentioning

confidence: 99%

Cis-regulatory elements used to control gene expression in plants

Biłas

Szafran

Hnatuszko-Konka

et al. 2016

Plant Cell Tiss Organ Cult

210

113

View full text Add to dashboard Cite

“…The VNTR lies in the 3 0 -UTR, which is located downstream of the protein coding sequence and does not directly affect protein structure. However, the 3 0 -UTR may have a role in influencing posttranscriptional gene expression, for example, through transcript cleavage, mRNA stability, and localization or polyadenylation (Barrett et al, 2012), or remote effects from regulatory regions of other genes (Dekker, 2008).…”

Section: Pharmacogenetic Findingsmentioning

confidence: 99%

Methylphenidate Effects on Brain Activity as a Function of SLC6A3 Genotype and Striatal Dopamine Transporter Availability

Kasparbauer

Rujescu²,

Riedel

et al. 2014

Neuropsychopharmacol

View full text Add to dashboard Cite

We pharmacologically challenged catecholamine reuptake, using methylphenidate, to investigate its effects on brain activity during a motor response inhibition task as a function of the 3 0 -UTR variable number of tandem repeats (VNTR) polymorphism of the dopamine transporter (DAT) gene (SLC6A3) and the availability of DATs in the striatum. We measured the cerebral hemodynamic response of 50 healthy males during a Go/No-Go task, a measure of cognitive control, under the influence of 40 mg methylphenidate and placebo using 3T functional magnetic resonance imaging. Subjects were grouped into 9-repeat (9R) carriers and 10/10 homozygotes on the basis of the SLC6A3 VNTR. During successful no-go trials compared with oddball trials, methylphenidate induced an increase of blood oxygen level-dependent (BOLD) signal for carriers of the SLC6A3 9R allele but a decrease in 10/10 homozygotes in a thalamocortical network. The same pattern was observed in caudate and inferior frontal gyrus when successful no-go trials were compared with successful go trials. We additionally investigated in a subset of 35 participants whether baseline striatal DAT availability, ascertained with 123 I-FP-CIT single photon emission computed tomography, predicted the amount of methylphenidate-induced change in hemodynamic response or behavior. Striatal DAT availability was nominally greater in 9R carriers compared with 10/10 homozygotes (d ¼ 0.40), in line with metaanalyses, but did not predict BOLD or behavioral changes following MPH administration. We conclude that the effects of acute MPH administration on brain activation are dependent on DAT genotype, with 9R carriers showing enhanced BOLD following administration of a prodopaminergic compound.

show abstract

Regulation of eukaryotic gene expression by the untranslated gene regions and other non-coding elements

Cited by 491 publications

References 199 publications

The Modulatory Effects of the Polymorphisms in GLA 5′-Untranslated Region Upon Gene Expression Are Cell-Type Specific

The Modulatory Effects of the Polymorphisms in GLA 5′-Untranslated Region Upon Gene Expression Are Cell-Type Specific

Cis-regulatory elements used to control gene expression in plants

Methylphenidate Effects on Brain Activity as a Function of SLC6A3 Genotype and Striatal Dopamine Transporter Availability

Contact Info

Product

Resources

About