Epstein-Barr virus super-enhancer eRNAs are essential for MYC oncogene expression and lymphoblast proliferation

Proc Natl Acad Sci U S A. 2016 Dec 6;113(49):14121-14126. doi: 10.1073/pnas.1616697113. Epub 2016 Nov 18.

Abstract

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.

Keywords: Epstein–Barr virus; MYC; eRNA; super-enhancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Cycle Proteins
  • Cell Line
  • Endonucleases
  • Enhancer Elements, Genetic*
  • Herpesvirus 4, Human / physiology*
  • Host-Pathogen Interactions*
  • Humans
  • Lymphoproliferative Disorders / virology*
  • Nuclear Proteins / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Transcription Factors / metabolism

Substances

  • BRD4 protein, human
  • Cell Cycle Proteins
  • MYC protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors
  • Endonucleases
  • SND1 protein, human