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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. Examination of H3k27ac and RNA pol II in Striatum by deep sequencing

ORGANISM(S): Mus musculus

SUBMITTER: Karine Merienne 

PROVIDER: E-GEOD-59570 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Neuronal identity genes regulated by super-enhancers are preferentially down-regulated in the striatum of Huntington's disease mice.

Achour Mayada M   Le Gras Stéphanie S   Keime Céline C   Parmentier Frédéric F   Lejeune François-Xavier FX   Boutillier Anne-Laurence AL   Néri Christian C   Davidson Irwin I   Merienne Karine K  

Human molecular genetics 20150317 12

Huntington's disease (HD) is a neurodegenerative disease associated with extensive down-regulation of genes controlling neuronal function, particularly in the striatum. Whether altered epigenetic regulation underlies transcriptional defects in HD is unclear. Integrating RNA-sequencing (RNA-seq) and chromatin-immunoprecipitation followed by massively parallel sequencing (ChIP-seq), we show that down-regulated genes in HD mouse striatum associate with selective decrease in H3K27ac, a mark of activ  ...[more]

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