Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

The effects on transcriptome from absence of Spt4/Supt4h by RNA-seq

ABSTRACT: We have done RNAseq analyses in yeast and in rat and mouse striatal neurons. The experiments in yeast examine globally the physiological effects of spt4 deletion on the transcriptome. The experiments in neurons examine the global effects of supt4 knockdown to a cellular level (i.e., 50% knockdown) that we have shown prevents toxicity of variant Htt protein by interfering with transcription of extended CAG repeats. The results of both sets of experiments indicate that absent spt4 function has limited effects on overall transcription. Moreover, the mammalian cell experiments indicate that supt4h knockdown to a cellular level that alters production of transcripts containing long CAG repeats has minimal effects on normal genes, supporting the notion that anti-supt4h measures may prove useful in combating trinucleotide repeat diseases. RNA-seq was done for two yeast WT strain W303 and two spt4 deletion strain spt4M-bM-^HM-^F as biological repeats, and rat ST14A cells and mouse HdhQ7/Q7 cells after transfection with NC control siRNA or Supt4h siRNA

ORGANISM(S): Rattus norvegicus

SUBMITTER: Ning Deng

PROVIDER: E-GEOD-33497 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Spt4 is selectively required for transcription of extended trinucleotide repeats.

Liu Chia-Rung CR Chang Chuang-Rung CR Chern Yijuang Y Wang Tzu-Han TH Hsieh Wen-Chieh WC Shen Wen-Chuan WC Chang Chi-Yuan CY Chu I-Chieh IC Deng Ning N Cohen Stanley N SN Cheng Tzu-Hao TH

Cell 20120201 4

Lengthy trinucleotide repeats encoding polyglutamine (polyQ) stretches characterize the variant proteins of Huntington's disease and certain other inherited neurological disorders. Using a phenotypic screen to identify events that restore functionality to polyQ proteins in S. cerevisiae, we discovered that transcription elongation factor Spt4 is required to transcribe long trinucleotide repeats located either in ORFs or nonprotein-coding regions of DNA templates. Mutation of SPT4 selectively dec ...[more]

PMID: 22341442

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Project description:HuntingtonÂs disease (HD) is a devastating neurodegenerative disease, with out effective treatment. Despite significant advances, our understanding of how an expanded CAG repeat in the amino terminus of the large ubiquitously expressed HD gene product remains incomplete. Augmented adult neurogenesis in response to acute and chronic injury, including HuntingtonÂs disease, has been demonstrated, but its role development, disease, and recovery is largely unknown, as are the factors controlling it. The HD gene product, huntingtin (htt) is know to interact with a number of transcription factors which subsequently influence gene expression. Understanding the factors involved in controlling neurogenesis in response to disease would bridge a significant knowledge gap and have tremendous therapeutic potential. We propose to identify transcripts responsible for CAG repeat facilitated neurogenesis. Our hypothesis is that expanded CAG repeats in the HuntingtonÂs disease gene facilitates neurogenesis by altering transcription of genes critical in neurogenesis. We have developed a model in which mouse embryonic stem cells (ESC) with expanded CAG repeats have facilitated neurogenesis. In this model more ESC with expanded CAG repeats transition to neuronal precursors and then develop into mature neurons more rapidly than control ESC. We propose to compare the gene expression profiles between ESC with expanded CAG repeats and control ESCs on days 4 and 6 of neuronal differentiation. Initial studies indicate that key transcriptional differences are occurring at these time points. Control ECS and a an ESC line with150 CAG repeats will be differentiated in triplicate, and RNA isolated form each replicate. It is anticipated that comparison of gene expression between the control and CAG repeat lines at each time point will identify transcripts involved in CAG repeat facilitated neurogenesis. Observed differences at day 4 may be more relevant to the transition from ESC to neuronal precursor whereas differences at day 6 may be more relevant to the neuronal precursor to neuron transition.

Project description:Huntingtons disease (HD) is a devastating neurodegenerative disease, with out effective treatment. Despite significant advances, our understanding of how an expanded CAG repeat in the amino terminus of the large ubiquitously expressed HD gene product remains incomplete. Augmented adult neurogenesis in response to acute and chronic injury, including Huntingtons disease, has been demonstrated, but its role development, disease, and recovery is largely unknown, as are the factors controlling it. The HD gene product, huntingtin (htt) is know to interact with a number of transcription factors which subsequently influence gene expression. Understanding the factors involved in controlling neurogenesis in response to disease would bridge a significant knowledge gap and have tremendous therapeutic potential. We propose to identify transcripts responsible for CAG repeat facilitated neurogenesis. Our hypothesis is that expanded CAG repeats in the Huntingtons disease gene facilitates neurogenesis by altering transcription of genes critical in neurogenesis. We have developed a model in which mouse embryonic stem cells (ESC) with expanded CAG repeats have facilitated neurogenesis. In this model more ESC with expanded CAG repeats transition to neuronal precursors and then develop into mature neurons more rapidly than control ESC. We propose to compare the gene expression profiles between ESC with expanded CAG repeats and control ESCs on days 4 and 6 of neuronal differentiation. Initial studies indicate that key transcriptional differences are occurring at these time points. Control ECS and a an ESC line with150 CAG repeats will be differentiated in triplicate, and RNA isolated form each replicate. It is anticipated that comparison of gene expression between the control and CAG repeat lines at each time point will identify transcripts involved in CAG repeat facilitated neurogenesis. Observed differences at day 4 may be more relevant to the transition from ESC to neuronal precursor whereas differences at day 6 may be more relevant to the neuronal precursor to neuron transition. Keywords: time-course

Dataset Information

The effects on transcriptome from absence of Spt4/Supt4h by RNA-seq

Publications

Spt4 is selectively required for transcription of extended trinucleotide repeats.

Similar Datasets

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