دورية أكاديمية
TAZ-CAMTA1 and YAP-TFE3 alter the TAZ/YAP transcriptome by recruiting the ATAC histone acetyltransferase complex
| العنوان: | TAZ-CAMTA1 and YAP-TFE3 alter the TAZ/YAP transcriptome by recruiting the ATAC histone acetyltransferase complex |
|---|---|
| المؤلفون: | Nicole Merritt, Keith Garcia, Dushyandi Rajendran, Zhen-Yuan Lin, Xiaomeng Zhang, Katrina A Mitchell, Nicholas Borcherding, Colleen Fullenkamp, Michael S Chimenti, Anne-Claude Gingras, Kieran F Harvey, Munir R Tanas |
| المصدر: | eLife, Vol 10 (2021) |
| بيانات النشر: | eLife Sciences Publications Ltd |
| سنة النشر: | 2021 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | hippo pathway, sarcomas, chimeric transcription factors, fusion proteins, epigenetics, ATAC complex, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Epithelioid hemangioendothelioma (EHE) is a vascular sarcoma that metastasizes early in its clinical course and lacks an effective medical therapy. The TAZ-CAMTA1 and YAP-TFE3 fusion proteins are chimeric transcription factors and initiating oncogenic drivers of EHE. A combined proteomic/genetic screen in human cell lines identified YEATS2 and ZZZ3, components of the Ada2a-containing histone acetyltransferase (ATAC) complex, as key interactors of both fusion proteins despite the dissimilarity of the C terminal fusion partners CAMTA1 and TFE3. Integrative next-generation sequencing approaches in human and murine cell lines showed that the fusion proteins drive a unique transcriptome by simultaneously hyperactivating a TEAD-based transcriptional program and modulating the chromatin environment via interaction with the ATAC complex. Interaction of the ATAC complex with both fusion proteins indicates that it is a key oncogenic driver and unifying enzymatic therapeutic target for this sarcoma. This study presents an approach to mechanistically dissect how chimeric transcription factors drive the formation of human cancers. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | https://elifesciences.org/articles/62857Test; https://doaj.org/toc/2050-084XTest; e62857; https://doaj.org/article/f5236ab6208a49dc9d2f318dd8878eeeTest |
| DOI: | 10.7554/eLife.62857 |
| الإتاحة: | https://doi.org/10.7554/eLife.62857Test https://doaj.org/article/f5236ab6208a49dc9d2f318dd8878eeeTest |
| رقم الانضمام: | edsbas.EA175F8B |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2050084X |
|---|---|
| DOI: | 10.7554/eLife.62857 |