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Updated: Jan 26, 2026

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Why the c-Fos/c-Jun complex is extremely conserved: An in vitro evolution exploration by combining cDNA display and
Shou-Kai Kang1, Xin-Yi Chu1, Tian Tian1
1Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan, China.
Abstract:
Transcriptional regulation involves a series of sophisticated protein-protein and protein-DNA interactions (PPI and PDI). Some transcriptional complexes, such as c-Fos/c-Jun and their binding DNA fragments, have been conserved over the past one billion years. Considering the thermodynamic principle for transcriptional complex formation, we hypothesized that the c-Fos/c-Jun complex may represent a thermodynamic summit in the evolutionary space. To test this, we invented a new method, termed One-Pot-seq, which combines cDNA display and proximity ligation to analyse PPI/PDI complexes simultaneously. We found that the wild-type c-Fos/c-Jun complex is indeed the most thermodynamically stable relative to various mutants of c-Fos/c-Jun and binding DNA fragments. Our method also provides a universal approach to detect transcriptional complexes and explore transcriptional regulation mechanisms.
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