Analysis 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.
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.
Marullo
Manuela
M
Department of Pharmacological Sciences and Center for Stem Cell Research, University of Milan, Milan, Italy.
Valenza
Marta
M
Mariotti
Caterina
C
Di Donato
Stefano
S
Cattaneo
Elena
E
Zuccato
Chiara
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002469:Cell Separation; D002478:Cells, Cultured; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D018450:Disease Progression; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D047468:Immunoprecipitation; D008214:Lymphocytes / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D000099229:RE1-Silencing Transcription Factor
D002843:Chromatin; D012333:RNA, Messenger; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor