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Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington’s disease [ChIP-seq]

ABSTRACT: Huntington neurodegenerative disease (HD) is associated with extensive down-regulation of neuronal genes. We show preferential down-regulation of super-enhancer-regulated neuronal function genes in the striatum of HD mice. Striatal super-enhancers display extensive H3K27 acetylation within gene bodies and drive transcription characterized by low levels of paused RNAPII. Down-regulation of gene expression is associated with diminished H3K27 acetylation and RNAPII recruitment. Striatal super-enhancers are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Thus, enhancer topography and transcription dynamics are major parameters determining the propensity of a gene to be deregulated in a neurodegenerative disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE59570 | GEO | 2015/04/01

SECONDARY ACCESSION(S): PRJNA255650

REPOSITORIES: GEO

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Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington’s disease [ChIP-seq]

Project description:Huntington neurodegenerative disease (HD) is associated with extensive down-regulation of neuronal genes. We show preferential down-regulation of super-enhancer-regulated neuronal function genes in the striatum of HD mice. Striatal super-enhancers display extensive H3K27 acetylation within gene bodies and drive transcription characterized by low levels of paused RNAPII. Down-regulation of gene expression is associated with diminished H3K27 acetylation and RNAPII recruitment. Striatal super-enhancers are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Thus, enhancer topography and transcription dynamics are major parameters determining the propensity of a gene to be deregulated in a neurodegenerative disease. Examination of H3k27ac and RNA pol II in Striatum by deep sequencing

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Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington’s disease [RNA-seq]

Project description:Huntington neurodegenerative disease (HD) is associated with extensive down-regulation of neuronal genes. We show preferential down-regulation of super-enhancer-regulated neuronal function genes in the striatum of HD mice. Striatal super-enhancers display extensive H3K27 acetylation within gene bodies and drive transcription characterized by low levels of paused RNAPII. Down-regulation of gene expression is associated with diminished H3K27 acetylation and RNAPII recruitment. Striatal super-enhancers are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Thus, enhancer topography and transcription dynamics are major parameters determining the propensity of a gene to be deregulated in a neurodegenerative disease. RNA profiles in Striatum of WT and R6/1 mice by deep sequencing using Illumina HiSeq 2000.

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