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Series GSE88894 Query DataSets for GSE88894
Status Public on Nov 20, 2018
Title TFEB controls vascular development by regulating the proliferation of endothelial cells (TFEB ChIp-seq)
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The role of the transcription factor EB (TFEB) in the control of cellular functions, including in vascular bed, is mostly thought to be the regulation of lysosomal biogenesis and autophagic flux. While this is its best-known function, we report here the ability of TFEB to orchestrate a non-canonical program involved in the control of cell-cycle and VEGFR2 pathway in the developing vasculature. In endothelial cells, TFEB deletion halts proliferation by inhibiting the CDK4/Rb pathway, which regulates the cell cycle G1-S transition. In an attempt to overcome this limit, cells compensate by increasing the amount of VEGFR2 on the plasma membrane through a microRNA-mediated mechanism and the control of its membrane trafficking. TFEB transactivates the miR-15a/16-1 cluster, which limits the stability of the VEGFR2 transcript, and negatively modulates the expression of MYO1C, which regulates VEGFR2 delivery to the cell surface. In TFEB knocked-down cells, the reduced and increased amount respectively of miR-15a/16-1 and MYO1C result in the overexpression on plasmamembrane of VEGFR2, which however shows low signaling strength. Using endothelial loss-of-function Tfeb mouse mutants, we present evidence of defects in fetal and newborn mouse vasculature caused by the reduced endothelial proliferation and by the anomalous function of VEGFR2 pathway. Thus, this study revealed a new and unreported function of TFEB that expands its role beyond the regulation of autophagic pathway in the vascular system.
Overall design ChIP-seq TFEB and IgG in HUVEC cells
Contributor(s) Doronzo G, Astanina E, Cora' D, Neri F, Oliviero S, Federico B
Citation(s) 30591554
Submission date Oct 18, 2016
Last update date May 15, 2019
Contact name Davide Cora'
Phone +390321660631
Organization name Piemonte Orientale University and IRCCS Candiolo Cancer Institute
Department Dept. of Oncology
Lab Vascular Oncology
Street address Str. Prov. 142 Km. 3.95
City Candiolo
State/province TO
ZIP/Postal code I-10060
Country Italy
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (2)
GSM2354031 ChIP-seq IgG
GSM2354032 ChIP-seq TFEB
This SubSeries is part of SuperSeries:
GSE88896 TFEB controls vascular development by regulating the proliferation of endothelial cells
BioProject PRJNA349029
SRA SRP091717

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE88894_RAW.tar 470.0 Kb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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