TY - JOUR
T1 - Taz-camta1 and yap-tfe3 alter the taz/yap transcriptome by recruiting the atac histone acetyltransferase complex
AU - Merritt, Nicole
AU - Garcia, Keith
AU - Rajendran, Dushyandi
AU - Lin, Zhen Yuan
AU - Zhang, Xiaomeng
AU - Mitchell, Katrina M.
AU - Borcherding, Nicholas
AU - Fullenkamp, Colleen
AU - Chimenti, Michael S.
AU - Gingras, Anne Claude
AU - Harvey, Kieran F.
AU - Tanas, Munir R.
N1 - Publisher Copyright:
© 2021, eLife Sciences Publications Ltd. All rights reserved.
PY - 2021/4
Y1 - 2021/4
N2 - 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 Ada2acontaining 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.
AB - 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 Ada2acontaining 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.
UR - http://www.scopus.com/inward/record.url?scp=85105756991&partnerID=8YFLogxK
U2 - 10.7554/ELIFE.62857
DO - 10.7554/ELIFE.62857
M3 - Article
C2 - 33913810
AN - SCOPUS:85105756991
SN - 2050-084X
VL - 10
JO - eLife
JF - eLife
M1 - e62857
ER -