Cited by 44Genetics and Neurodevelopmental DisordersEpigenetics and DNA MethylationGenetic Neurodegenerative Diseases

Modest reactivation of the mutant FMR1 gene by valproic acid is accompanied by histone modifications but not DNA demethylation

Tabolacci, Elisabetta, De Pascalis, Ivana, Accadia, Maria, Terracciano, Alessandra, Moscato, Umberto, Chiurazzi, Pietro, Neri, Giovanni·2008·Pharmacogenetics and Genomics

Abstract

Fragile X syndrome (FXS), the leading cause of inherited mental retardation, is due to expansion and methylation of a CGG sequence in the FMR1 gene, which result in its silencing. We previously demonstrated a reactivation of FMR1 in FXS cells treated with the DNA demethylating drug 5-azadeoxycytidine, and, to a lesser extent, with the histone deacetylating drug butyrate. To identify other reactivating drugs, we now treated three FXS lymphoblastoid cell lines with valproic acid (VPA), a well-known antiepileptic drug, causing histone deacetylase inhibition and, possibly, DNA demethylation. After VPA treatment, FMR1-mRNA levels were low and FMRP protein was undetectable. The gene remained methylated, whereas histones were acetylated and a modest variation of histone methylation was observed. These results confirm the histone hyperacetylating effect of VPA but do not support its putative DNA demethylation activity. The primary role of DNA demethylation in the reactivation of the FMR1 gene was confirmed.

Integrity signals

Registry

Crossref · 10.1097/fpc.0b013e32830500a1

Cites

11 of 11 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Valproic acid is known as a reactivator of silenced genes and appeared to be a weak reactivator of full mutation.

    “The third tested compound is valproic acid (101), which is already known as a reactivator of silenced genes (102) that appeared to be a weak reactivator of FM (103).”

Cites

Flagged first, then by citations

1 of the 12 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Tabolacci, E., De Pascalis, I., Accadia, M., Terracciano, A., Moscato, U., Chiurazzi, P., & Neri, G.
Affiliations
Università Cattolica del Sacro Cuore (IT)
Corresponding author
Neri, Giovanni
Venue
Pharmacogenetics and Genomics
Published
2008-08
Volume
18
Issue
8
Pages
738-741
ISSN
1744-6872 (ISSN-L)
OpenAlex
W2087016730
Cited by
44
References
12
Citations by year
2024: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 8 · 2015: 2 · 2014: 3 · 2013: 5 · 2012: 4
FWCI
1.71
Type
journal article
Language
en
Open access
closed
Locations
  • Pharmacogenetics and Genomics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Keywords
FMR1 gene, fragile X syndrome, valproic acid, histone deacetylase inhibition, histone acetylation, histone methylation, DNA methylation, CGG repeat expansion, gene silencing, FMRP, butyrate, gene reactivation, lymphoblastoid cell lines
MeSH terms
Acetylation, Cell Line, Female, Gene Expression Regulation, Histones, Humans, Male, RNA, Messenger, Valproic Acid, DNA Methylation, Chromatin Immunoprecipitation, Fragile X Messenger Ribonucleoprotein 1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review