One Billion Years of bZIP Transcription Factor Evolution: Conservation and Change in Dimerization and DNA-Binding Site Specificity

Abstract

The genomic era has revealed that the large repertoire of observed animal phenotypes is dependent on changes in the expression patterns of a finite number of genes, which are mediated by a plethora of transcription factors (TFs) with distinct specificities. The dimerization of TFs can also increase the complexity of a genetic regulatory network manifold, by combining a small number of monomers into dimers with distinct functions. Therefore, studying the evolution of these dimerizing TFs is vital for understanding how complexity increased during animal evolution. We focus on the second largest family of dimerizing TFs, the basic-region leucine zipper (bZIP), and infer when it expanded and how bZIP DNA-binding and dimerization functions evolved during the major phases of animal evolution. Specifically, we classify the metazoan bZIPs into 19 families and confirm the ancient nature of at least 13 of these families, predating the split of the cnidaria. We observe fixation of a core dimerization network in the last common ancestor of protostomes-deuterostomes. This was followed by an expansion of the number of proteins in the network, but no major dimerization changes in interaction partners, during the emergence of vertebrates. In conclusion, the bZIPs are an excellent model with which to understand how DNA binding and protein interactions of TFs evolved during animal evolution.

The Multi-zinc Finger Protein ZNF217 Contacts DNA through a Two-finger Domain

“…4 Two further residues that were identified in our NMR analysis are zinc binding residues (His-489 and Cys-504), and their direct involvement in DNA binding is difficult to ascertain via mutagenesis because of their structural importance. The equivalent histidine in other zinc finger-DNA complexes does lie near the DNA backbone and commonly makes an electrostatic interaction with a phosphate group (2).…”

BACH1 Is a Specific Repressor of HMOX1 That Is Inactivated by Arsenite

“…In response to oxidative stress, such as that mediated by arsenite, cells induce a battery of protective antioxidant enzymes of which HMOX1 and thioredoxin reductase-1 (TXNRD1) are two well recognized members. This antioxidant response depends on stabilization and nuclear accumulation of the oxidant-activated transcription factor NFE2L2 (nuclear factor (erythroid-derived 2)-like 2, previously known as NRF2) (18 -20), a basic region leucine zipper factor belonging to the MAF family of transcriptional regulators (21). To become transcriptionally active, nuclear NFE2L2 must heterodimerize with small MAF proteins and bind ARE enhancer motifs (22).…”

Basic Leucine Zipper (bZIP) Domain Transcription Factor MBZ1 Regulates Cell Wall Integrity, Spore Adherence, and Virulence in Metarhizium robertsii

“…Much of our knowledge about the features and functions of transcription factors (TFs), 2 including a group of structurally and functionally related members containing the conserved basic leucine zipper (bZIP) domain, comes from the discovery and study of AP-1 (activating protein 1) (1). The bZIP TFs are one of the largest families of dimerizing TFs and are widely distributed in the genomes of all eukaryotes (2).…”

“…The bZIP TFs are one of the largest families of dimerizing TFs and are widely distributed in the genomes of all eukaryotes (2). The prototypical bZIP TF was first discovered over 30 years ago in humans (3), and members are now classified into 19 families regulating a plethora of biological functions, including the cell cycle, development, reproduction, metabolism, and programmed cell death (2). Besides animals, bZIP-type TFs have also been well characterized in plants by mediating pathogen defense, abiotic stress response, hormone signaling, energy metabolism, and senescence (4).…”