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Long-range Pitx2c Enhancer Promoter Interactions Prevent Predisposition to Atrial Fibrillation [ChIP-seq]

ABSTRACT: Long-range Pitx2c Enhancer Promoter Interactions Prevent Predisposition to Atrial Fibrillation [ChIP-seq]

PROVIDER: PRJNA576256 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10240124_1.fastq.gz	Fastqsanger.gz
	SRR10240124_2.fastq.gz	Fastqsanger.gz
	SRR10240125_1.fastq.gz	Fastqsanger.gz
	SRR10240125_2.fastq.gz	Fastqsanger.gz
	SRR10240126_1.fastq.gz	Fastqsanger.gz

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Long-range Pitx2c Enhancer Promoter Interactions Prevent Predisposition to Atrial Fibrillation [RNA-seq]

Project description:Genome-wide association studies (GWAS) have found that increased risk for atrial fibrillation (AF), the most common type of arrhythmia in humans, is associated with non-coding sequence variants located in proximity to the PITX2 homeobox gene. Using cardiomyocyte-specific epigenomic and comparative genomic analyses, we identified two AF-associated enhancers neighboring PITX2 with varying degrees of conservation in mice. Pitx2c promoter directly contacted the AF-associated enhancer regions. CRISPR/Cas9 mediated deletion of a 20 kb long topologically engaged enhancer lead to reduced Pitx2c transcription and AF predisposition. Allele-specific ChIP-seq and CUT&RUN experiments showed that long-range interaction of this AF-associated region with the Pitx2c promoter was required for maintenance of the Pitx2c promoter chromatin state. Moreover, long-range looping was mediated by CTCF, as the genetic disruption of an intronic CTCF binding site caused decreased Pitx2c cardiac expression, AF predisposition, and reduced active chromatin marks on Pitx2. Our findings reveal that AF risk variants located at 4q25 reside in genomic regions possessing long-range transcriptional regulatory functions directed at PITX2

2019-10-08 | GSE138529 | GEO

Long-range Pitx2c Enhancer Promoter Interactions Prevent Predisposition to Atrial Fibrillation [ChIP-seq]

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Long-range Pitx2c Enhancer Promoter Interactions Prevent Predisposition to Atrial Fibrillation

Project description:Long-range Pitx2c Enhancer Promoter Interactions Prevent Predisposition to Atrial Fibrillation

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Long-range Pitx2c Enhancer Promoter Interactions Prevent Predisposition to Atrial Fibrillation [RNA-seq]

Project description:Long-range Pitx2c Enhancer Promoter Interactions Prevent Predisposition to Atrial Fibrillation [RNA-seq]

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Long-range Pitx2c Enhancer Promoter Interactions Prevent Predisposition to Atrial Fibrillation

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

2019-10-07 | GSE138530 | GEO

Atrial Fibrillation After Surgery for Colorectal Cancer

Project description:This study will report the incidence of atrial fibrillation after elective colorectal cancer resection in the over 65 age group. This will be used to validate a risk model for the development of post-operative atrial fibrillation. Eligible patients will undergo electrocardiogram based screening for atrial fibrillation, as well as brain natriuretic peptide tests prior to surgery. They will undergo 24 hour holter monitor prior to surgery, and at 30 and 90 days following surgery. The primary outcome will be occurrence of atrial fibrillation within 90 days of surgery. Secondary outcomes include quality of life change, use of hospital services for atrial fibrillation, and complications of atrial fibrillation. This will be used to validate the pre-existing model for prediction of atrial fibrillation.

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Long-range <i>Pitx2c</i> enhancer-promoter interactions prevent predisposition to atrial fibrillation.

Project description:Genome-wide association studies found that increased risk for atrial fibrillation (AF), the most common human heart arrhythmia, is associated with noncoding sequence variants located in proximity to PITX2 Cardiomyocyte-specific epigenomic and comparative genomics uncovered 2 AF-associated enhancers neighboring PITX2 with varying conservation in mice. Chromosome conformation capture experiments in mice revealed that the Pitx2c promoter directly contacted the AF-associated enhancer regions. CRISPR/Cas9-mediated deletion of a 20-kb topologically engaged enhancer led to reduced Pitx2c transcription and AF predisposition. Allele-specific chromatin immunoprecipitation sequencing on hybrid heterozygous enhancer knockout mice revealed that long-range interaction of an AF-associated region with the Pitx2c promoter was required for maintenance of the Pitx2c promoter chromatin state. Long-range looping was mediated by CCCTC-binding factor (CTCF), since genetic disruption of the intronic CTCF-binding site caused reduced Pitx2c expression, AF predisposition, and diminished active chromatin marks on Pitx2 AF risk variants located at 4q25 reside in genomic regions possessing long-range transcriptional regulatory functions directed at PITX2.

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