Abstract
Normal growth and development, as well as adaptive responses to various intracellular and environmental stresses, are tightly controlled by transcriptional networks. The evolutionarily conserved genomic sequences across species highlights the architecture of such certain regulatory elements. Among them, one of the most conserved transcription factors is the basic-region leucine zipper (bZIP) family. Herein, we have performed phylogenetic analysis of these bZIP proteins and found, to our surprise, that there exist a few homologous proteins of the family members Jun, Fos, ATF2, BATF, C/EBP and CNC (cap’n’collar) in either viruses or bacteria, albeit expansion and diversification of this bZIP superfamily have occurred in vertebrates from metazoan. Interestingly, a specific group of bZIP proteins is identified, designated Nach (Nrf and CNC homology), because of their strong conservation with all the known CNC and NF-E2 p45 subunit-related factors Nrf1 and Nrf2. Further experimental evidence has also been provided, revealing that Nach1 and Nach2 from the marine bacteria exert distinctive functions, when compared with human Nrf1 and Nrf2, in the transcriptional regulation of antioxidant response element (ARE)-battery genes. Collectively, further insights into these Nach/CNC-bZIP subfamily transcription factors provide a novel better understanding of distinct biological functions of these factors expressed in distinct species from the marine bacteria to humans.
Highlights
The evolutionarily conserved sequences across species may be attributed to at least two main reasons, i.e., conserved helices and consensus regulatory elements existing especially among developmental process-related transcription factor (TF) genes in living organisms [2]
The more basic-region leucine zipper (bZIP) proteins were identified in vertebrates, e.g., the human (Homo sapiens) up to 53 bZIP proteins, six of which belong to the CNC-bZIP subfamily
This work deciphers the early origin of such a large bZIP superfamily, which is inferred to originate from putative infected viral and/or bacterial cognate genes transferred to the last common ancestor, that had long evolved from prokaryotic to eukaryotic genes and undergone the natural selection with multiple independent expansions during its evolutionary process
Summary
The evolutionarily conserved sequences across species may be attributed to at least two main reasons, i.e., conserved helices (such as in 16S rRNA [1]) and consensus regulatory elements existing especially among developmental process-related transcription factor (TF) genes in living organisms [2]. To ensure that only the fittest of life forms can survive and maintain a robust homoeostasis being established during the nature selection [3], their transcriptional networks that are composed of distinct transcription factor families play essential roles in regulating the expression of different sets of cognate target genes [4] Such ability of TFs is manifested by their specific cis-regulatory DNA sequences, e.g., antioxidant response elements (AREs) and activating protein-1 (AP-1)-binding site, in order to control the transcriptional expression of cognate target genes and display relevant functional performances in many ways [5,6]. The LZ region is composed of heptad repeats of leucine or other bulky hydrophobic residues exactly occupied at the “d” positions, and mediates dimerization of bZIP proteins [13,14]
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