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Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy [ATAC-seq]

ABSTRACT: Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy [ATAC-seq]

PROVIDER: PRJNA862069 | ENA |

REPOSITORIES: ENA

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Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy [WES]

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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Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy [RNA-seq]

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Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy [CUT&Tag]

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Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy [ATAC-seq]

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Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy

Project description:Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy

| PRJNA862064 | ENA

Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy [WES]

Project description:Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy [WES]

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Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy [RNA-seq]

Project description:Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy [RNA-seq]

| PRJNA862070 | ENA

Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy [CUT&Tag]

Project description:Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy [CUT&Tag]

| PRJNA862071 | ENA

Recruitment of ETS1 to activated accessible regions promotes cilia genes transcriptional program in ciliopathy

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

2022-07-28 | GSE209662 | GEO

Recruitment of transcription factor ETS1 to activated accessible regions promotes the transcriptional program of cilia genes.

Project description:Defects in cilia genes, which are critical for cilia formation and function, can cause complicated ciliopathy syndromes involving multiple organs and tissues; however, the underlying regulatory mechanisms of the networks of cilia genes in ciliopathies remain enigmatic. Herein, we have uncovered the genome-wide redistribution of accessible chromatin regions and extensive alterations of expression of cilia genes during Ellis-van Creveld syndrome (EVC) ciliopathy pathogenesis. Mechanistically, the distinct EVC ciliopathy-activated accessible regions (CAAs) are shown to positively regulate robust changes in flanking cilia genes, which are a key requirement for cilia transcription in response to developmental signals. Moreover, a single transcription factor, ETS1, can be recruited to CAAs, leading to prominent chromatin accessibility reconstruction in EVC ciliopathy patients. In zebrafish, the collapse of CAAs driven by ets1 suppression subsequently causes defective cilia proteins, resulting in body curvature and pericardial oedema. Our results depict a dynamic landscape of chromatin accessibility in EVC ciliopathy patients, and uncover an insightful role for ETS1 in controlling the global transcriptional program of cilia genes by reprogramming the widespread chromatin state.

| S-EPMC10359609 | biostudies-literature

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