ArticleBMC molecular biology2003
Fragile X (CGG)n repeats induce a transcriptional repression in cis upon a linked promoter: evidence for a chromatin mediated effect.
Article in BMC molecular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 14 citations in OpenAlex.
- Of Men and Mice: Modeling the Fragile X Syndrome.Frontiers in molecular neuroscience · 2018Article
- The promise and perils of HDAC inhibitors in neurodegeneration.Annals of clinical and translational neurology · 2015Review
- Epigenetics in nucleotide repeat expansion disorders.Seminars in neurology · 2011Review
- The distribution of repressive histone modifications on silenced FMR1 alleles provides clues to the mechanism of gene silencing in fragile X syndrome.Human molecular genetics · 2010Article
- NF-Y, AP2, Nrf1 and Sp1 regulate the fragile X-related gene 2 (FXR2).The Biochemical journal · 2006Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundExpansion of an unstable (CGG)n repeat to over 200 triplets within the promoter region of the human FMR1 gene leads to extensive local methylation and transcription silencing, resulting in the loss of FMRP protein and the development of the clinical features of fragile X syndrome. The causative link between (CGG)n expansion, methylation and gene silencing is unknown, although gene silencing is associated with extensive changes to local chromatin architecture.
resultsIn order to determine the direct effects of increased repeat length on gene transcription in a chromatin context, we have examined the influence of FMR1 (CGG)n repeats upon transcription from the HSV thymidine kinase promoter in the Xenopus laevis oocyte. We observe a reduction in mRNA production directly associated with increasing repeat length, with a 90% reduction in mRNA production from arrays over 100 repeats in length. Using a kinetic approach, we show that this transcriptional repression is concomitant with chromatin maturation and, using in vitro transcription, we show that chromatin formation is a fundamental part of the repressive pathway mediated by (CGG)n repeats. Using Trichostatin A, a histone deacetylase inhibitor, we show reactivation of the silenced promoter.
conclusionsThus, isolated fragile X associated (CGG)n repeat arrays can exert a modifying and transcriptionally repressive influence over adjacent promoters and this repressive phenomenon is, in part, mediated by histone deacetylation.
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