The ETS transcription factors ELK1 and GABPA regulate different gene networks to control MCF10A breast epithelial cell migration

PLoS One. 2012;7(12):e49892. doi: 10.1371/journal.pone.0049892. Epub 2012 Dec 20.

Abstract

Members of the ETS transcription factor family often target the same binding regions and hence have the potential to regulate the same genes and downstream biological processes. However, individual family members also preferentially bind to other genomic regions, thus providing the potential for controlling distinct transcriptional programmes and generating specific biological effects. The ETS transcription factor ELK1 controls cell migration in breast epithelial cells through targeting a cohort of genes, independently from another family member GABPA, and therefore achieves biological specificity. Here, we demonstrate that GABPA also controls cell migration in breast epithelial cells. However, GABPA controls the expression of a different network of target genes to ELK1. Both direct and indirect target genes for GABPA are identified and amongst the direct targets we confirm the importance of RAC1 and KIF20A for cell migration. Therefore, although ELK1 and GABPA ultimately control the same biological process, they do so by regulating different cohorts of target genes associated with cytoskeletal functions and cell migration control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Movement*
  • Cytoskeleton / genetics
  • GA-Binding Protein Transcription Factor / metabolism*
  • Gene Expression Regulation*
  • Gene Regulatory Networks*
  • Humans
  • Mammary Glands, Human / cytology*
  • Mammary Glands, Human / metabolism
  • Transcription, Genetic
  • ets-Domain Protein Elk-1 / metabolism*

Substances

  • ELK1 protein, human
  • GA-Binding Protein Transcription Factor
  • GABPA protein, human
  • ets-Domain Protein Elk-1