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Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington's disease

ABSTRACT: Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington's disease

PROVIDER: PRJNA255648 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1519950.fastq.gz	Fastqsanger.gz
	SRR1519960.fastq.gz	Fastqsanger.gz
	SRR1519951.fastq.gz	Fastqsanger.gz
	SRR1519961.fastq.gz	Fastqsanger.gz
	SRR1519952.fastq.gz	Fastqsanger.gz

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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

2015-04-01 | E-GEOD-59570 | biostudies-arrayexpress

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.

2015-04-01 | E-GEOD-59571 | biostudies-arrayexpress

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

2015-04-01 | GSE59571 | GEO

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

2015-04-01 | GSE59570 | GEO

Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington's disease

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-04-01 | GSE59572 | GEO

Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington's disease

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-04-01 | E-GEOD-59572 | biostudies-arrayexpress

Mus musculus

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

| PRJNA255650 | ENA

Mus musculus

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

| PRJNA255649 | ENA

Transcriptional deregulation during osteoclastic differentiation due to diuron exposure affects preferentially super-enhancers regulated genes

Project description:Transcriptional deregulation during osteoclastic differentiation due to diuron exposure affects preferentially super-enhancers regulated genes

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Stably-paused genes revealed through inhibition of transcription initiation by the TFIIH inhibitor Triptolide

Project description:Transcription by RNA Polymerase II (Pol II) in metazoan is regulated in several steps, including preinitiation complex (PIC) formation, initiation, Pol II escape, productive elongation, cotranscriptional RNA-processing and termination. Genome-wide studies have demonstrated that the phenomenon of promoter-bound Pol II pausing is widespread, especially for genes involved in developmental and stimulus-responsive pathways. However, a mechanistic understanding of the paused Pol II states at promoters is limited. For example, at a global level, it’s unclear to what extent the engaged paused Pol II is stably tethered to the promoter or undergoes rapid cycles of initiation and termination. Here we used the small molecule Triptolide (TPL), an XPB/TFIIH inhibitor, to block transcriptional initiation followed by measuring Pol II occupancy by ChIP-seq. This inhibition of initiation enables us to investigate different states of paused Pol II. Specifically, our global analysis reveals that most genes with paused Pol II, as defined by pausing index, show significant clearance of Pol II during the period of TPL treatment. Our study further identifies a group of genes with unexpectedly stably-paused Pol II, with unchanged Pol II occupancy even after one hour of inhibition of initiation. This group of genes constitutes a small portion of all paused genes defined by the conventional criterion of pausing index. These findings could pave the way for evaluating the contribution of different elongation/pausing factors on different states of Pol II pausing in developmental and other stimulus-responsive pathways. ChIP-Seq of total/Ser5P Pol II in HCT116 cells treated with DMSO or TPL in serum starvation/activation or normal conditions. Nascent RNA-seq in HCT116 cells treated with DMSO or TPL in starved condition.

2015-01-05 | E-GEOD-63314 | biostudies-arrayexpress

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