Project description:TAZ-CAMTA1 is a defining genetic aberration in the vascular cancer epithelioid hemangioendothelioma. We generated a novel transgenic mouse that expresses TAZ-CAMTA1 in endothelial cells. These mice develop vascular tumors in the lung and die by average on day 40. We isolated GFP + endothelial cells from three five-week old TRE-TAZ-CAMTA1;Cdh5-tTA;TRE-GFP mice and subjected these endothelial cells to scRNA-seq via the 10X genomics platform
Project description:TAZ-CAMTA1 is a defining genetic aberration in the vascular cancer epithelioid hemangioendothelioma. We studied the transcriptome of TAZ-CAMTA1 and compared it to that of control or activated TAZ (TAZ4A)-expressing endothelial cells. We utilized an immortalized, mouse endothelial cell line known as MS1. We present and make available the first RNA-sequencing data of TAZ-CAMTA1's transcriptome in endothelial cells
Project description:TAZ-CAMTA1 (TC) is one of two fusion proteins known to define Epithelioid Hemangioendothelioma (EHE), a rare vascular sarcoma. It is thought that TC expression represents the initiating event in EHE development. We have developed a model for studying EHE through the differentiation of mESCs into primary endothelial cells, in which TC and GFP expression is induced by the addition of doxycycline. The purpose of this RNA-seq experiment was to determine transcriptomic differences between endothelial cells expressing TC or not. To this end, endothelial cells were treated with doxycycline for 24 hours to induce TC expression, then sorted by flow cytometry into GFP high, low and negative populations whereby GFP is a marker for TC expression. These three populations along with uninduced control endothelial cells were then subject to RNA-seq. Analysis involved comparing the transcriptomes of the TC high, low and negative endothelial cell populations to the uninduced controls.
Project description:The WWTR1(TAZ)-CAMTA1 and YAP1-TFE3 gene fusions are disease defining gene alterations for epithelioid hemangioendothelioma, a vascular cancer. The resultant fusion proteins fuse the C terminus of CAMTA1 and TFE3 in frame to the N terminus of TAZ and YAP, respectively. An unbiased BioID-mass spectrometry/RNAi screen identified YEATS2 and ZZZ3 as components of the Ada2a-containing histone acetyltransferase complex and key interactors of both TAZ-CAMTA1 and YAP-TFE3. An integrative NGS approach including RNA-Seq, ChIP-Seq, and ATAC-Seq showed TAZ-CAMTA1 and YAP-TFE3 transcriptional programs overlap with TAZ and YAP but also drive expression of a novel transcriptome.
Project description:The WWTR1(TAZ)-CAMTA1 and YAP1-TFE3 gene fusions are disease defining gene alterations for epithelioid hemangioendothelioma, a vascular cancer. The resultant fusion proteins fuse the C terminus of CAMTA1 and TFE3 in frame to the N terminus of TAZ and YAP, respectively. An unbiased BioID-mass spectrometry/RNAi screen identified YEATS2 and ZZZ3 as components of the Ada2a-containing histone acetyltransferase complex and key interactors of both TAZ-CAMTA1 and YAP-TFE3. An integrative NGS approach including RNA-Seq, ChIP-Seq, and ATAC-Seq showed TAZ-CAMTA1 and YAP-TFE3 transcriptional programs overlap with TAZ and YAP but also drive expression of a novel transcriptome. The altered transcriptional program of the fusion proteins owing to altered DNA binding as well as shifts in the chromatin landscape.
Project description:The WWTR1(TAZ)-CAMTA1 and YAP1-TFE3 gene fusions are disease defining gene alterations for epithelioid hemangioendothelioma, a vascular cancer. The resultant fusion proteins fuse the C terminus of CAMTA1 and TFE3 in frame to the N terminus of TAZ and YAP, respectively. An unbiased BioID-mass spectrometry/RNAi screen identified YEATS2 and ZZZ3 as components of the Ada2a-containing histone acetyltransferase complex and key interactors of both TAZ-CAMTA1 and YAP-TFE3. An integrative NGS approach including RNA-Seq, ChIP-Seq, and ATAC-Seq showed TAZ-CAMTA1 and YAP-TFE3 transcriptional programs overlap with TAZ and YAP but also drive expression of a novel transcriptome. The altered transcriptional program of the fusion proteins owing to altered DNA binding as well as shifts in the chromatin landscape.
Project description:The WWTR1(TAZ)-CAMTA1 and YAP1-TFE3 gene fusions are disease defining gene alterations for epithelioid hemangioendothelioma, a vascular cancer. The resultant fusion proteins fuse the C terminus of CAMTA1 and TFE3 in frame to the N terminus of TAZ and YAP, respectively. An unbiased BioID-mass spectrometry/RNAi screen identified YEATS2 and ZZZ3 as components of the Ada2a-containing histone acetyltransferase complex and key interactors of both TAZ-CAMTA1 and YAP-TFE3. An integrative NGS approach including RNA-Seq, ChIP-Seq, and ATAC-Seq showed TAZ-CAMTA1 and YAP-TFE3 transcriptional programs overlap with TAZ and YAP but also drive expression of a novel transcriptome. The altered transcriptional program of the fusion proteins owing to altered DNA binding as well as shifts in the chromatin landscape.
Project description:The WWTR1(TAZ)-CAMTA1 and YAP1-TFE3 gene fusions are disease defining gene alterations for epithelioid hemangioendothelioma, a vascular cancer. The resultant fusion proteins fuse the C terminus of CAMTA1 and TFE3 in frame to the N terminus of TAZ and YAP, respectively. An unbiased BioID-mass spectrometry/RNAi screen identified YEATS2 and ZZZ3 as components of the Ada2a-containing histone acetyltransferase complex and key interactors of both TAZ-CAMTA1 and YAP-TFE3. An integrative NGS approach validating the chromatin occupancy of TAZ-CAMTA1 and YAP-TFE3 with distal regulatory elements, such as enhancer regions marked by the presence of H3K27ac marks. The altered transcriptional program of the fusion proteins owing to altered DNA binding as well as shifts in the chromatin landscape.
Project description:The WWTR1(TAZ)-CAMTA1 and YAP1-TFE3 gene fusions are disease defining gene alterations for epithelioid hemangioendothelioma, a vascular cancer. The resultant fusion proteins fuse the C terminus of CAMTA1 and TFE3 in frame to the N terminus of TAZ and YAP, respectively. An unbiased BioID-mass spectrometry/RNAi screen identified YEATS2 and ZZZ3 as components of the Ada2a-containing histone acetyltransferase complex and key interactors of both TAZ-CAMTA1 and YAP-TFE3. An integrative NGS approach including RNA-Seq and ATAC-Seq showed that the differentially expressed genes in YAP-TFE3 cells with knockdown of YEATS2 or ZZZ3 are nested in regions of open chromatin unique to YAP-TFE3. The altered transcriptional program of the fusion proteins is modulated by the Ada2a-containing histone acetyltransferase complex.