Open AccessAnalysis of the Repressor Element‐1 Silencing Transcription Factor/Neuron‐Restrictive Silencer Factor Occupancy of Non‐Neuronal Genes in Peripheral Lymphocytes from Patients with Huntington's Disease
Author(s) -
Marullo Manuela,
Valenza Marta,
Mariotti Caterina,
Di Donato Stefano,
Cattaneo Elena,
Zuccato Chiara
Publication year - 2010
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2008.00249.x
Subject(s) - gene silencing , transcription factor , chromatin immunoprecipitation , repressor , biology , silencer , gene , genetics , promoter , gene expression , mechanical engineering , engineering , inlet
We have previously demonstrated that the transcription of neuronal repressor element‐1/neuron‐restrictive silencer element (RE1/NRSE)‐regulated genes is reduced in the brain of subjects with Huntington's disease (HD) as a result of increased binding of the repressor element‐1 silencing transcription factor/neuron‐restrictive silencer factor (REST/NRSF) to its RE1/NRSE targets. As specific non‐neuronal REST/NRSF‐regulated genes have been identified in the human genome, we exploited the possibility that the binding of REST/NRSF to its target RE1/NRSE sites may also be altered in the peripheral tissues of HD patients. Our results show that REST/NRSF occupancy is increased in lymphocytes from HD subjects, thus indicating for the first time that the activity of the RE1/NRSE sites is dysfunctional in vivo . Chromatin immunoprecipitation (ChIP) of the RE1/NRSE sites in lymphocytes may therefore be a reproducible, sensitive and specific means of searching for candidate markers of HD onset and progression.