TY - JOUR
T1 - Human accelerated region 1 noncoding RNA is repressed by REST in Huntington's disease
AU - Johnson, Rory
AU - Richter, Nadine
AU - Jauch, Ralf
AU - Gaughwin, Philip M.
AU - Zuccato, Chiara
AU - Cattaneo, Elena
AU - Stanton, Lawrence W.
PY - 2010/5
Y1 - 2010/5
N2 - In the neurons of Huntington's disease (HD) patients, gene regulatory networks are disrupted by aberrant nuclear localization of the master transcriptional repressor REST. Emerging evidence suggests that, in addition to protein-coding genes, noncoding RNAs (ncRNAs) may also contribute to neurodegenerative processes. To discover ncRNAs that are involved in HD, we screened genome-wide data for novel, noncoding targets of REST. This identified human accelerated region 1 (HAR1), a rapidly evolving cis-antisense locus that is specifically transcribed in the nervous system. We show that REST is targeted to the HAR1 locus by specific DNA regulatory motifs, resulting in potent transcriptional repression. Consistent with other REST target genes, HAR1 levels are significantly lower in the striatum of HD patients compared with unaffected individuals. These data represent further evidence that noncoding gene expression changes accompany neurodegeneration in Huntington's disease.
AB - In the neurons of Huntington's disease (HD) patients, gene regulatory networks are disrupted by aberrant nuclear localization of the master transcriptional repressor REST. Emerging evidence suggests that, in addition to protein-coding genes, noncoding RNAs (ncRNAs) may also contribute to neurodegenerative processes. To discover ncRNAs that are involved in HD, we screened genome-wide data for novel, noncoding targets of REST. This identified human accelerated region 1 (HAR1), a rapidly evolving cis-antisense locus that is specifically transcribed in the nervous system. We show that REST is targeted to the HAR1 locus by specific DNA regulatory motifs, resulting in potent transcriptional repression. Consistent with other REST target genes, HAR1 levels are significantly lower in the striatum of HD patients compared with unaffected individuals. These data represent further evidence that noncoding gene expression changes accompany neurodegeneration in Huntington's disease.
KW - Long noncoding RNA
KW - Neurodegeneration
KW - Neuron-restrictive silencing factor
KW - RE1-silencing transcription factor
KW - Regulation
UR - https://www.scopus.com/pages/publications/77952940922
U2 - 10.1152/physiolgenomics.00019.2010
DO - 10.1152/physiolgenomics.00019.2010
M3 - Article
C2 - 20179156
AN - SCOPUS:77952940922
SN - 1094-8341
VL - 41
SP - 269
EP - 274
JO - Physiological Genomics
JF - Physiological Genomics
IS - 3
ER -