Runx3-mediated transcriptional program in cytotoxic lymphocytes

PLoS One. 2013 Nov 13;8(11):e80467. doi: 10.1371/journal.pone.0080467. eCollection 2013.

Abstract

The transcription factor Runx3 is highly expressed in CD8(+) T and NK cytotoxic lymphocytes and is required for their effective activation and proliferation but molecular insights into the transcription program regulated by Runx3 in these cells are still missing. Using Runx3-ChIP-seq and transcriptome analysis of wild type vs. Runx3(-/-) primary cells we have now identified Runx3-regulated genes in the two cell types at both resting and IL-2-activated states. Runx3-bound genomic regions in both cell types were distantly located relative to gene transcription start sites and were enriched for RUNX and ETS motifs. Bound genomic regions significantly overlapped T-bet and p300-bound enhancer regions in Runx3-expressing Th1 helper cells. Compared to resting cells, IL-2-activated CD8(+) T and NK cells contain three times more Runx3-regulated genes that are common to both cell types. Functional annotation of shared CD8(+) T and NK Runx3-regulated genes revealed enrichment for immune-associated terms including lymphocyte activation, proliferation, cytotoxicity, migration and cytokine production, highlighting the role of Runx3 in CD8(+) T and NK activated cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Core Binding Factor Alpha 3 Subunit / genetics*
  • Enhancer Elements, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation* / drug effects
  • Histones / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-2 / pharmacology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Knockout
  • Nucleotide Motifs
  • Position-Specific Scoring Matrices
  • Protein Binding
  • Resting Phase, Cell Cycle / genetics
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*
  • Transcription Factor AP-1 / metabolism
  • Transcription Initiation Site
  • Transcription, Genetic*

Substances

  • Core Binding Factor Alpha 3 Subunit
  • Histones
  • Interleukin-2
  • Transcription Factor AP-1

Associated data

  • GEO/GSE50131

Grant support

This work was supported by grants from Israel Science Foundation individual grants to YG and D. Levanon. URL: http://isf.org.il/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.