Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster

ABSTRACT: Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster

PROVIDER: PRJNA761668 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR15809403_1.fastq.gz	Fastqsanger.gz
	SRR15809403_2.fastq.gz	Fastqsanger.gz
	SRR15809404_1.fastq.gz	Fastqsanger.gz
	SRR15809404_2.fastq.gz	Fastqsanger.gz
	SRR15809405_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 32

Similar Datasets

Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster

Project description:Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster

| PRJNA761667 | ENA

Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster

Project description:Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster

| PRJNA761660 | ENA

Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster

Project description:Single cell RNA-Seq and ATAC-Seq in mouse E10.5 multipotent pancreatic progenitors (MPCs) and single cell ATAC-Seq of mouse E13.5 pancreas.

2022-06-30 | GSE183673 | GEO

Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster.

Project description:Sequence variants in cis-acting enhancers are important for polygenic disease, but their role in Mendelian disease is poorly understood. Redundancy between enhancers that regulate the same gene is thought to mitigate the pathogenic impact of enhancer mutations. Recent findings, however, have shown that loss-of-function mutations in a single enhancer near PTF1A cause pancreas agenesis and neonatal diabetes. Using mouse and human genetic models, we show that this enhancer activates an entire PTF1A enhancer cluster in early pancreatic multipotent progenitors. This leading role, therefore, precludes functional redundancy. We further demonstrate that transient expression of PTF1A in multipotent progenitors sets in motion an epigenetic cascade that is required for duct and endocrine differentiation. These findings shed insights into the genome regulatory mechanisms that drive pancreas differentiation. Furthermore, they reveal an enhancer that acts as a regulatory master key and is thus vulnerable to pathogenic loss-of-function mutations.

| S-EPMC9426562 | biostudies-literature

Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster

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

2022-06-30 | GSE183674 | GEO

Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster

Project description:Genome-wide maps of H3K27ac, Mediator and PTF1A binding in stage-4 human multipotent pancreatic progenitor cells

2022-06-30 | GSE183672 | GEO

A conserved notochord enhancer controls pancreas development in vertebrates

Project description:A conserved notochord enhancer controls pancreas development in vertebrates

| PRJEB36984 | ENA

Duplications disrupt chromatin architecture and rewire GPR101-enhancer communication in X-linked acrogigantism

Project description:Duplications disrupt chromatin architecture and rewire GPR101-enhancer communication in X-linked acrogigantism

| PRJNA794841 | ENA

Auricular Malformations Driven by Copy Number Variations in a Hierarchical Enhancer Cluster and Dominant Enhancer Recapitulates Human Pathogenesis

Project description:Enhancers, through the combinatorial action of transcription factors (TFs), dictate both the spatial specificity and the levels of gene expression, and their aberrations can result in diseases. While HMX1 downstream enhancer is associated to ear malformations, the mechanisms underlying bilateral constricted ear (BCE) remain unclear. Here, we identify a copy number variation (CNV) containing three enhancers—collectively termed the positional identity hierarchical enhancer cluster (PI-HEC)—that drives BCE by coordinately regulating HMX1 expression. Each enhancer exhibits distinct activity-location-structure features, and the dominant enhancer with high mobility group (HMG)-box and homeodomain TF motifs modulating its activity and specificity, respectively. Mouse models demonstrate that neural crest-derived fibroblasts with aberrant Hmx1 expression in the basal pinna, along with ectopic distal pinna expression, disrupt outer ear development, affecting cartilage, muscle, and epidermis. Our findings elucidate mammalian ear morphogenesis and underscore the complexity of synergistic regulation among enhancers and between enhancers and transcription factors.

2025-03-31 | GSE293403 | GEO

Auricular Malformations Driven by Copy Number Variations in a Hierarchical Enhancer Cluster and Dominant Enhancer Recapitulates Human Pathogenesis

2024-05-01 | GSE263087 | GEO