title: Repressor element-1 silencing transcription factor (REST) is present in human control and Huntington's disease neurones.
abstract: OBJECTIVE
  The repressor element-1 silencing transcription factor/neurone-restrictive silencer factor (REST/NRSF) is a master regulator of neuronal gene expression. REST/NRSF functions by recruiting other cofactors to genomic loci that contain the repressor element 1/neurone restrictive silencer element (RE1/NRSE) binding motif. In brain, demonstration of REST protein presence in neurones has remained controversial. However, RE1/NRSE containing neuronal genes are actively modulated and REST dysregulation is implicated in Huntington's disease (HD). We aimed to investigate REST distribution in autopsy brain from control and HD patients.
  
  
  METHODS
  Brain tissues from six controls and six HD cases (Vonsattel grade 3 and 4) were investigated using immunohistochemical analysis.
  
  
  RESULTS
  REST was present in neurones and glial cells of the cortex, caudate nucleus, hippocampus and cerebellum. REST labelling was mainly cytoplasmic in neurones while preferential nuclear staining of REST was found in glial cells. We also found that REST and huntingtin (HTT) colocalize in human neurones. Low levels of cytoplasmic REST were detected in neurones of the HD cortex and caudate but no direct relationship between decreased neuronal REST expression and disease grade was observed.
  
  
  CONCLUSIONS
  These data support the notion of REST presence in human brain neurones and glial cells and indicate the importance of developing compounds able to restore REST-regulated transcription of neuronal genes in HD.
authors.affiliation: Neuro-Bio-Oncology Research Center, Policlinico di Monza Foundation, Vercelli; Consorzio per le Neuroscienze, University of Pavia, Pavia.
authors.forename: Davide
authors.initials: D
authors.lastname: Schiffer
authors.forename: Valentina
authors.initials: V
authors.lastname: Caldera
authors.forename: Marta
authors.initials: M
authors.lastname: Mellai
authors.forename: Paola
authors.initials: P
authors.lastname: Conforti
authors.forename: Elena
authors.initials: E
authors.lastname: Cattaneo
authors.forename: Chiara
authors.initials: C
authors.lastname: Zuccato
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D012097:Repressor Proteins / Q000032:analysis*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C086055:HTT protein, human
keywords: Huntington's disease; REST; human brain; huntingtin; neurones