The ETS Transcription Factors ELK1 and GABPA Regulate Different Gene Networks to Control MCF10A Breast Epithelial Cell Migration

Zaneta Odrowaz,Andrew D Sharrocks,Shree Ram Singh

doi:10.1371/journal.pone.0049892

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.

Highlights

Eukaryotic transcription factors are grouped into families based on their common DNA binding domains
GABPA controls cell migration We previously demonstrated that depletion of the ETS
The GABPA-dependent gene regulatory network The observation that GABPA plays a role in controlling cell migration was unexpected, as we previously showed that ELK1 controls this process in MCF10A cells, and it does this through a network of target genes in a manner that is independent of GABPA [7]

Summary

Introduction

Eukaryotic transcription factors are grouped into families based on their common DNA binding domains. Given that there are 28 ETS family members in mammals (reviewed in [2,3]) and that they possess a similar binding potential it is unclear how biological specificity is achieved. Insights into this have been provided by several genome-wide ChIP-seq/ChIP-chip studies, where it is clear that there is substantial overlap in DNA binding in vivo, individual family members preferentially bind to subsets of sites. This study confirmed the hypothesis that a specific biological effect can be elicited by the binding of a single family member, in this case ELK1, to a series of target genes that are not targeted by other family members

Methods

Results

Conclusion