Abstract

The Activator Protein-1 transcription factor family (AP-1) transcriptional complex is historically defined as an early response group of transcription factors formed by dimeric complexes of the Jun, Fos, Atf, and Maf bZIP proteins that control cell proliferation and differentiation by regulating gene expression. It has been greatly investigated in many model organisms across metazoan evolution. Nevertheless, its complexity and variability of action made its multiple functions difficult to be defined. Here, we place the foundations for understanding the complexity of AP-1 transcriptional members in tunicates. We investigated the gene members of this family in the ascidian Ciona robusta and identified single copies of Jun, Fos, Atf3, Atf2/7, and Maf bZIP-related factors that could have a role in the formation of the AP-1 complex. We highlight that mesenchyme is a common cellular population where all these factors are expressed during embryonic development, and that, moreover, Fos shows a wider pattern of expression including also notochord and neural cells. By ectopic expression in transgenic embryos of Jun and Fos genes alone or in combination, we investigated the phenotypic alterations induced by these factors and highlighted a degree of functional conservation of the AP-1 complex between Ciona and vertebrates. The lack of gene redundancy and the first pieces of evidence of conserved functions in the control of cell movements and structural organization exerted by these factors open the way for using Ciona as a helpful model system to uncover the multiple potentialities of this highly complex family of bZIP transcription factors.

Highlights

  • It is commonly recognized that the complexity of organisms does not always directly correlate with the number of genes in its genome

  • One of the best ways of creating a wider possibility of regulatory responses is through the formation of transcription factor (TF) dimers, with specific DNA-binding properties, that allows the definition of novel control circuits (Klemm et al, 1998)

  • The entire protein collection of C. robusta has undergone a comprehensive functional annotation to better characterize all the genes classified as bZIP members related to Jun and Fos

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Summary

Introduction

It is commonly recognized that the complexity of organisms does not always directly correlate with the number of genes in its genome. The AP-1 complex collectively describes a group of structurally and functionally related TFs of the Jun (Jun, JunB, and JunD) and Fos protein families (Fos, FosB, Fra-1, and Fra-2) and some members of the Atf (Atf, Atf-2, and Atf-3) and Jdp (Jdp-1 and Jdp-2) subfamilies. These factors share structural similarities and form homo- and heterodimeric complexes among them. All the combinations of AP-1 complexes bind a consensus sequence along the DNA (5 -TGAG/CTCA3 ), known as the 12-O–tetradecanoylphorbol-13-acetate (TPA)-responsive element (TRE) (Angel and Karin, 1991), and control both basal and inducible transcription of several genes containing the AP-1-binding sites in their regulatory sequences

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