Human accelerated region 1 noncoding RNA is repressed by REST in Huntington's disease

2010 ◽  
Vol 41 (3) ◽  
pp. 269-274 ◽  
Author(s):  
Rory Johnson ◽  
Nadine Richter ◽  
Ralf Jauch ◽  
Philip M. Gaughwin ◽  
Chiara Zuccato ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Transcriptional Repression ◽  
Noncoding Rna ◽  
Regulatory Networks ◽  
Target Genes ◽  
Protein Coding ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Dna Regulatory Motifs

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.

C04 Protein coding tandem repeat in TCERG1 modifies huntington’s disease onset

2021 ◽  
Author(s):  
Sergey Lobanov ◽  
Branduff McAllister ◽  
Mia McDade-Kumar ◽  
Jong-Min Lee ◽  
Marcy MacDonald ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Tandem Repeat ◽  
Disease Onset ◽  
Protein Coding

scholarly journals Role of co-regulators in metabolic and transcriptional actions of thyroid hormone

2016 ◽  
Vol 56 (3) ◽  
pp. R73-R97 ◽  
Author(s):  
Inna Astapova
Keyword(s):  
Thyroid Hormone ◽  
Transcriptional Repression ◽  
Target Genes ◽  
Thyroid Hormone Receptor ◽  
Retinoic Acid Receptor ◽  
Specific Response ◽  
Physiological Processes ◽  
Genome Wide ◽  
Wide Range ◽  
And Function

Thyroid hormone (TH) controls a wide range of physiological processes through TH receptor (TR) isoforms. Classically, TRs are proposed to function as tri-iodothyronine (T3)-dependent transcription factors: on positively regulated target genes, unliganded TRs mediate transcriptional repression through recruitment of co-repressor complexes, while T3binding leads to dismissal of co-repressors and recruitment of co-activators to activate transcription. Co-repressors and co-activators were proposed to play opposite roles in the regulation of negative T3target genes and hypothalamic–pituitary–thyroid axis, but exact mechanisms of the negative regulation by TH have remained elusive. Important insights into the roles of co-repressors and co-activators in different physiological processes have been obtained using animal models with disrupted co-regulator function. At the same time, recent studies interrogating genome-wide TR binding have generated compelling new data regarding effects of T3, local chromatin structure, and specific response element configuration on TR recruitment and function leading to the proposal of new models of transcriptional regulation by TRs. This review discusses data obtained in various mouse models with manipulated function of nuclear receptor co-repressor (NCoR or NCOR1) and silencing mediator of retinoic acid receptor and thyroid hormone receptor (SMRT or NCOR2), and family of steroid receptor co-activators (SRCs also known as NCOAs) in the context of TH action, as well as insights into the function of co-regulators that may emerge from the genome-wide TR recruitment analysis.

scholarly journals Genome-wide loss of 5-hmC is a novel epigenetic feature of Huntington's disease

2013 ◽  
Vol 22 (18) ◽  
pp. 3641-3653 ◽  
Author(s):  
Fengli Wang ◽  
Yeran Yang ◽  
Xiwen Lin ◽  
Jiu-Qiang Wang ◽  
Yong-Sheng Wu ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Genome Wide ◽  
Epigenetic Feature

scholarly journals Mismatch Repair Genes Mlh1 and Mlh3 Modify CAG Instability in Huntington's Disease Mice: Genome-Wide and Candidate Approaches

PLoS Genetics ◽  
2013 ◽  
Vol 9 (10) ◽  
pp. e1003930 ◽  
Author(s):  
Ricardo Mouro Pinto ◽  
Ella Dragileva ◽  
Andrew Kirby ◽  
Alejandro Lloret ◽  
Edith Lopez ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mismatch Repair ◽  
Mismatch Repair Genes ◽  
Genome Wide ◽  
Repair Genes

scholarly journals Transcriptional regulatory networks underlying gene expression changes in Huntington's disease

2018 ◽  
Vol 14 (3) ◽  
Author(s):  
Seth A Ament ◽  
Jocelynn R Pearl ◽  
Jeffrey P Cantle ◽  
Robert M Bragg ◽  
Peter J Skene ◽  
...  
Keyword(s):  
Gene Expression ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory

scholarly journals Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

2017 ◽  
Vol 16 (9) ◽  
pp. 701-711 ◽  
Author(s):  
Davina J Hensman Moss ◽  
Antonio F Pardiñas ◽  
Douglas Langbehn ◽  
Kitty Lo ◽  
Blair R Leavitt ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Association Study ◽  
Huntington’S Disease ◽  
Disease Progression ◽  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Genome-wide identification and comparison of differentially expressed profiles of miRNAs and lncRNAs with associated ceRNA networks in the gonads of Chinese soft-shelled turtle, Pelodiscus sinensis

2019 ◽  
Author(s):  
Xiao Ma ◽  
Shuangshuang Cen ◽  
Luming Wang ◽  
Chao Zhang ◽  
Limin Wu ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Regulatory Networks ◽  
Target Genes ◽  
Expression Profiles ◽  
Integrated Analysis ◽  
Regulation Mechanism ◽  
Pelodiscus Sinensis ◽  
Specific Expression ◽  
Protein Coding ◽  
Protein Coding Genes

Abstract Abstract Background: Gonad is the major factor affecting the animal reproduction. The regulation mechanism of protein coding genes expression involved reproduction is still remains to be elucidated. Increasing evidence has shown that ncRNAs play key regulatory roles in gene expression in many life processes. The roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in reproduction had been investigated in some species. However, the regulation patterns of miRNA and lncRNA in sex biased expression of protein coding genes remains to be elucidated. In this study, we performed an integrated analysis of miRNA, messenger RNA (mRNA), and lncRNA expression profiles to explore their regulatory patterns in the female ovary and male testis of the soft-shelled turtle, Pelodiscus sinensis. Results: We identified 10 796 mature miRNAs, 44 678 mRNAs, and 58 923 lncRNAs in the testis and ovary. A total of 16 817 target genes were identified for miRNAs. Of these, 11 319 mRNAs, 10 495 lncRNAs, and 633 miRNAs were expressed differently. The predicted target genes of these differential expression (DE) miRNAs and lncRNAs included genes related to reproduction regulation. Furthermore, we found that 5 408 DElncRNAs and 186 DE miRNAs showed sex-specific expression. Of these, 3 miRNAs and 917 lncRNAs were testis specific and 186 DEmiRNAs and 4 491 DElncRNAs were ovary specific. We constructed compete endogenous lncRNA-miRNA-mRNA networks using bioinformatics, including 273 DEmRNAs, 5 730 DEmiRNAs, and 2 945 DElncRNAs. The target genes for the different expressed of miRNAs and lncRNAs included Wt1, Creb3l2, Gata4, Wnt2, Nr5a1, Hsd17, Igf2r, H2afz, Lin52, Trim71, Zar1, and Jazf1, etc. Conclusions: In animals, miRNA and lncRNA regulate the reproduction process, including the regulation of oocyte maturation and spermatogenesis. Considering their importance, the identified miRNAs, lncRNAs, and their targets in P. sinensis might be useful for genome editing to produce higher quality aquaculture animals. A thorough understanding of ncRNA-based cellular regulatory networks will aid in the improvement of P. sinensis reproduction traits for aquaculture.

scholarly journals Huntington's Disease: Genome-wide Neuroprotection Screening Goes Viral

Neuron ◽  
2020 ◽  
Vol 106 (1) ◽  
pp. 4-6
Author(s):  
C.Y. Daniel Lee ◽  
X. William Yang
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Genome Wide
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