Lkb1 interacts with a ciliopathy complex to regulate inflammation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA339988 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4054614_1.fastq.gz | Fastqsanger.gz | |||
| SRR4054614_2.fastq.gz | Fastqsanger.gz | |||
| SRR4054615_1.fastq.gz | Fastqsanger.gz | |||
| SRR4054615_2.fastq.gz | Fastqsanger.gz | |||
| SRR4054616_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Ciliopathies comprise a spectrum of inherited disorders involving different organ systems such as the central nervous system, the skeleton, and the kidney1. The cilium is a hair-like organelle at the cell surface that acts as a sensor and signal transducer2. Many ciliopathy manifestations can be linked to deficient cilia function, yet it is unclear how a cilium defect results in nephronophthisis (NPHP), the most prevalent renal manifestation in children, characterized by inflammation, interstitial fibrosis, and renal cysts3. Here, we report that deletion of the serine threonine kinase Lkb1 in the mouse kidney results in cardinal features of nephronophthisis. An in-vivo proteomic interaction screen revealed ANKS3, a known interaction partner of the nephronophthisis protein NPHP1, and its interactor NEK7 as novel binding partners of LKB1. Lkb1 genetically interacts with Nphp1 in zebrafish. Unbiased transcriptional analysis in-vitro and in-vivo revealed that the chemokine CCL2 is upregulated in Lkb1 deficiency and is accompanied by recruitment of CCR2 expressing mononuclear cells in the kidney. CCL2 regulation requires NPHP1, ANKS3 and NEK7. These findings link LKB1 and ciliopathy proteins to immune regulation and explain how mutations in NPHP proteins result in fibrosis of the kidney.
2018-06-10 | GSE86009 | GEO
Project description:Ciliopathies comprise a spectrum of inherited disorders involving different organ systems such as the central nervous system, the skeleton, and the kidney1. The cilium is a hair-like organelle at the cell surface that acts as a sensor and signal transducer2. Many ciliopathy manifestations can be linked to deficient cilia function, yet it is unclear how a cilium defect results in nephronophthisis (NPHP), the most prevalent renal manifestation in children, characterized by inflammation, interstitial fibrosis, and renal cysts3. Here, we report that deletion of the serine threonine kinase Lkb1 in the mouse kidney results in cardinal features of nephronophthisis. An in-vivo proteomic interaction screen revealed ANKS3, a known interaction partner of the nephronophthisis protein NPHP1, and its interactor NEK7 as novel binding partners of LKB1. Lkb1 genetically interacts with Nphp1 in zebrafish. Unbiased transcriptional analysis in-vitro and in-vivo revealed that the chemokine CCL2 is upregulated in Lkb1 deficiency and is accompanied by recruitment of CCR2 expressing mononuclear cells in the kidney. CCL2 regulation requires NPHP1, ANKS3 and NEK7. These findings link LKB1 and ciliopathy proteins to immune regulation and explain how mutations in NPHP proteins result in fibrosis of the kidney.
2018-06-10 | GSE86010 | GEO
Project description:Lkb1 interacts with a ciliopathy complex to regulate inflammation (array)
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Project description:Lkb1 interacts with a ciliopathy complex to regulate inflammation (RNA-Seq)
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Project description:Defects in cilia genes that is critical in cilia formation and function can cause complicated ciliopathy syndromes involving multiple organs and tissues; however, the underlying regulatory mechanisms of cilia gene networks in ciliopathy are largely unknown. Here, we define the genome-wide redistribution of chromatin accessibilities and extensive divergence of cilia genes expression programs happened in ciliopathy. Mechanistically, the distinct ciliopathy-activated accessible regions (CAAs) are characterized to positively regulate robust changes of flanking cilia genes, which are a key transcriptional feature of cilia required for the response to developmental signals. Moreover, the single transcriptional factors, ETS1, can be recruited to CAAs thus prominently reconstructing chromatin accessibility in ciliopathy. CAAs collapse driven by ETS1 suppression subsequently cause defective cilia formation and impaired developmental signal transduction, which eventually develops ciliopathy phenotypes of short fins and pericardium edema in larval fishes. Therefore, our results depicted a dynamic landscape of chromatin accessibility in ciliopathy, and uncover an insightful role of ETS1 in controlling global cilia genes transcriptional program by reprogramming widespread chromatin state.
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Project description:Defects in cilia genes that is critical in cilia formation and function can cause complicated ciliopathy syndromes involving multiple organs and tissues; however, the underlying regulatory mechanisms of cilia gene networks in ciliopathy are largely unknown. Here, we define the genome-wide redistribution of chromatin accessibilities and extensive divergence of cilia genes expression programs happened in ciliopathy. Mechanistically, the distinct ciliopathy-activated accessible regions (CAAs) are characterized to positively regulate robust changes of flanking cilia genes, which are a key transcriptional feature of cilia required for the response to developmental signals. Moreover, the single transcriptional factors, ETS1, can be recruited to CAAs thus prominently reconstructing chromatin accessibility in ciliopathy. CAAs collapse driven by ETS1 suppression subsequently cause defective cilia formation and impaired developmental signal transduction, which eventually develops ciliopathy phenotypes of short fins and pericardium edema in larval fishes. Therefore, our results depicted a dynamic landscape of chromatin accessibility in ciliopathy, and uncover an insightful role of ETS1 in controlling global cilia genes transcriptional program by reprogramming widespread chromatin state.
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Project description:Defects in cilia genes that is critical in cilia formation and function can cause complicated ciliopathy syndromes involving multiple organs and tissues; however, the underlying regulatory mechanisms of cilia gene networks in ciliopathy are largely unknown. Here, we define the genome-wide redistribution of chromatin accessibilities and extensive divergence of cilia genes expression programs happened in ciliopathy. Mechanistically, the distinct ciliopathy-activated accessible regions (CAAs) are characterized to positively regulate robust changes of flanking cilia genes, which are a key transcriptional feature of cilia required for the response to developmental signals. Moreover, the single transcriptional factors, ETS1, can be recruited to CAAs thus prominently reconstructing chromatin accessibility in ciliopathy. CAAs collapse driven by ETS1 suppression subsequently cause defective cilia formation and impaired developmental signal transduction, which eventually develops ciliopathy phenotypes of short fins and pericardium edema in larval fishes. Therefore, our results depicted a dynamic landscape of chromatin accessibility in ciliopathy, and uncover an insightful role of ETS1 in controlling global cilia genes transcriptional program by reprogramming widespread chromatin state.
2022-07-28 | GSE209661 | GEO
Project description:Defects in cilia genes that is critical in cilia formation and function can cause complicated ciliopathy syndromes involving multiple organs and tissues; however, the underlying regulatory mechanisms of cilia gene networks in ciliopathy are largely unknown. Here, we define the genome-wide redistribution of chromatin accessibilities and extensive divergence of cilia genes expression programs happened in ciliopathy. Mechanistically, the distinct ciliopathy-activated accessible regions (CAAs) are characterized to positively regulate robust changes of flanking cilia genes, which are a key transcriptional feature of cilia required for the response to developmental signals. Moreover, the single transcriptional factors, ETS1, can be recruited to CAAs thus prominently reconstructing chromatin accessibility in ciliopathy. CAAs collapse driven by ETS1 suppression subsequently cause defective cilia formation and impaired developmental signal transduction, which eventually develops ciliopathy phenotypes of short fins and pericardium edema in larval fishes. Therefore, our results depicted a dynamic landscape of chromatin accessibility in ciliopathy, and uncover an insightful role of ETS1 in controlling global cilia genes transcriptional program by reprogramming widespread chromatin state.
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