Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Acetylated histones are associated with FMR1 in normal but not fragile X-syndrome cells

Acetylated histones are associated with FMR1 in normal but not fragile X-syndrome cells Mutation of FMR1 results in fragile X mental retardation 1 . The most common FMR1 mutation is expansion of a CGG repeat tract at the 5´ end of FMR1 (refs 2, 3, 4), which leads to cytosine methylation and transcriptional silencing 5,6 . Both DNA methylation and histone deacetylation have been associated with transcriptional inactivity 7,8,9 . The finding that the methyl cytosine-binding protein MeCP2 binds to histone deacetylases and represses transcription in vivo 10,11 supports a model in which MeCP2 recruits histone deacetylases to methylated DNA, resulting in histone deacetylation, chromatin condensation and transcriptional silencing 12 . Here we demonstrate that the 5´ end of FMR1 is associated with acetylated histones H3 and H4 in cells from normal individuals, but acetylation is reduced in cells from fragile X patients. Treatment of fragile X cells with 5-aza-2´-deoxycytidine (5-aza-dC) resulted in reassociation of acetylated histones H3 and H4 with FMR1 and transcriptional reactivation, whereas treatment with trichostatin A (TSA) led to almost complete acetylated histone H4 and little acetylated histone H3 reassociation with FMR1, as well as no detectable transcription. Our results represent the first description of loss of histone acetylation at a specific locus in human disease, and advance understanding of the mechanism of FMR1 transcriptional silencing. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Genetics Springer Journals

Acetylated histones are associated with FMR1 in normal but not fragile X-syndrome cells

Download PDF
4 pages

Loading next page...
 
/lp/springer-journals/acetylated-histones-are-associated-with-fmr1-in-normal-but-not-fragile-oz8snYQvNt

References (36)

Publisher
Springer Journals
Copyright
Copyright © 1999 by Nature America Inc.
Subject
Biomedicine; Biomedicine, general; Human Genetics; Cancer Research; Agriculture; Gene Function; Animal Genetics and Genomics
ISSN
1061-4036
eISSN
1546-1718
DOI
10.1038/8807
Publisher site
See Article on Publisher Site

Abstract

Mutation of FMR1 results in fragile X mental retardation 1 . The most common FMR1 mutation is expansion of a CGG repeat tract at the 5´ end of FMR1 (refs 2, 3, 4), which leads to cytosine methylation and transcriptional silencing 5,6 . Both DNA methylation and histone deacetylation have been associated with transcriptional inactivity 7,8,9 . The finding that the methyl cytosine-binding protein MeCP2 binds to histone deacetylases and represses transcription in vivo 10,11 supports a model in which MeCP2 recruits histone deacetylases to methylated DNA, resulting in histone deacetylation, chromatin condensation and transcriptional silencing 12 . Here we demonstrate that the 5´ end of FMR1 is associated with acetylated histones H3 and H4 in cells from normal individuals, but acetylation is reduced in cells from fragile X patients. Treatment of fragile X cells with 5-aza-2´-deoxycytidine (5-aza-dC) resulted in reassociation of acetylated histones H3 and H4 with FMR1 and transcriptional reactivation, whereas treatment with trichostatin A (TSA) led to almost complete acetylated histone H4 and little acetylated histone H3 reassociation with FMR1, as well as no detectable transcription. Our results represent the first description of loss of histone acetylation at a specific locus in human disease, and advance understanding of the mechanism of FMR1 transcriptional silencing.

Journal

Nature Genetics – Springer Journals

Published: May 1, 1999

There are no references for this article.