| Title: |
Modulation of nucleosome dynamics in Huntington’s disease |
| Authors: |
Edward C. Stack; Steven J. Del Signore; Ruth Luthi-carter; Byoung Y. Soh; Darlene R. Goldstein; Samantha Matson; Sarah Goodrich; Angela L. Markey; Kerry Cormier; Sean W. Hagerty; Karen Smith; Hoon Ryu; Robert J. Ferrante |
| Contributors: |
The Pennsylvania State University CiteSeerX Archives |
| Source: |
http://hmg.oxfordjournals.org/content/16/10/1164.full.pdf. |
| Publication Year: |
2007 |
| Collection: |
CiteSeerX |
| Description: |
Transcriptional dysregulation and aberrant chromatin remodeling are central features in the pathology of Huntington’s disease (HD). In order to more fully characterize these pathogenic events, an assessment of his-tone profiles and associated gene changes were performed in transgenic N171–82Q (82Q) and R6/2 HD mice. Analyses revealed significant chromatin modification, resulting in reduced histone acetylation with concomi-tant increased histone methylation, consistent with findings observed in HD patients. While there are no known interventions that ameliorate or arrest HD progression, DNA/RNA-binding anthracyclines may provide significant therapeutic potential by correcting pathological nucleosome changes and realigning transcrip-tion. Two such anthracyclines, chromomycin and mithramycin, improved altered nucleosome homeostasis in HD mice, normalizing the chromatin pattern. There was a significant shift in the balance between methyl-ation and acetylation in treated HD mice to that found in wild-type mice, resulting in greater acetylation of histone H3 at lysine 9 and promoting gene transcription. Gene expression profiling in anthracycline-treated HD mice showed molecular changes that correlate with disease correction, such that a subset of downregu-lated genes were upregulated with anthracycline treatment. Improved nucleosomal dynamics were concur-rent with a significant improvement in the behavioral and neuropathological phenotype observed in HD mice. These data show the ability of anthracycline compounds to rebalance epigenetic histone modification |
| Document Type: |
text |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.544.4174; http://hmg.oxfordjournals.org/content/16/10/1164.full.pdf |
| Availability: |
http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.544.4174; http://hmg.oxfordjournals.org/content/16/10/1164.full.pdf |
| Rights: |
Metadata may be used without restrictions as long as the oai identifier remains attached to it. |
| Accession Number: |
edsbas.4EF62F39 |
| Database: |
BASE |