期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：49
页码：14121-14126
DOI：10.1073/pnas.1616697113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceEBV infection causes African Burkitt's lymphoma; Hodgkin's disease; lymphomas in immune suppressed people, including HIV infected people; nasopharyngeal carcinoma; and [~]10% of gastric carcinomas. We recently found EBV super-enhancer (ESE) to be critical for lymphoblastoid cell (LCL) growth and survival. We now identified an ESE constituent, enhancer RNA (eRNA), that is important for ESE function. These eRNAs were activated by viral transactivator, EBV nuclear antigen 2 (EBNA2). MYC oncogene ESE eRNAs were able to enhance ESE activation of MYC expression and are essential for LCL growth. Targeting ESE eRNAs may lead to new therapeutics for EBV-associated malignancies. Epstein-Barr virus (EBV) super-enhancers (ESEs) are essential for lymphoblastoid cell (LCL) growth and survival. Reanalyses of LCL global run-on sequencing (Gro-seq) data found abundant enhancer RNAs (eRNAs) being transcribed at ESEs. Inactivation of ESE components, EBV nuclear antigen 2 (EBNA2) and bromodomain-containing protein 4 (BRD4), significantly decreased eRNAs at ESEs -428 and -525 kb upstream of the MYC oncogene transcription start site (TSS). shRNA knockdown of the MYC -428 and -525 ESE eRNA caused LCL growth arrest and reduced cell growth. Furthermore, MYC ESE eRNA knockdown also significantly reduced MYC expression, ESE H3K27ac signals, and MYC ESEs looping to MYC TSS. These data indicate that ESE eRNAs strongly affect cell gene expression and enable LCL growth.
