The fungal CCAAT-binding complex and HapX display highly variable but evolutionary conserved synergetic promoter-specific DNA recognition.
Nucleic Acids Res, 2020/04/17;48(7):3567-3590.
Furukawa T[1], Scheven MT[2], Misslinger M[3], Zhao C[1], Hoefgen S[4], Gsaller F[3], Lau J[1], Jöchl C[3], Donaldson I[1], Valiante V[4, 5], Brakhage AA[2, 5], Bromley MJ[1], Haas H[3], Hortschansky P[2]
Affiliations
PMID: 32086516DOI: 10.1093/nar/gkaa109
Impact factor: 19.16
Abstract
To sustain iron homeostasis, microorganisms have evolved fine-tuned mechanisms for uptake, storage and detoxification of the essential metal iron. In the human pathogen Aspergillus fumigatus, the fungal-specific bZIP-type transcription factor HapX coordinates adaption to both iron starvation and iron excess and is thereby crucial for virulence. Previous studies indicated that a HapX homodimer interacts with the CCAAT-binding complex (CBC) to cooperatively bind bipartite DNA motifs; however, the mode of HapX-DNA recognition had not been resolved. Here, combination of in vivo (genetics and ChIP-seq), in vitro (surface plasmon resonance) and phylogenetic analyses identified an astonishing plasticity of CBC:HapX:DNA interaction. DNA motifs recognized by the CBC:HapX protein complex comprise a bipartite DNA binding site 5'-CSAATN12RWT-3' and an additional 5'-TKAN-3' motif positioned 11-23 bp downstream of the CCAAT motif, i.e. occasionally overlapping the 3'-end of the bipartite binding site. Phylogenetic comparison taking advantage of 20 resolved Aspergillus species genomes revealed that DNA recognition by the CBC:HapX complex shows promoter-specific cross-species conservation rather than regulon-specific conservation. Moreover, we show that CBC:HapX interaction is absolutely required for all known functions of HapX. The plasticity of the CBC:HapX:DNA interaction permits fine tuning of CBC:HapX binding specificities that could support adaptation of pathogens to their host niches.
MeSH terms
AT Rich Sequence; Aspergillus fumigatus; Basic-Leucine Zipper Transcription Factors; Binding Sites; CCAAT-Binding Factor; DNA, Fungal; Evolution, Molecular; Fungal Proteins; Iron; Mutation; Nucleotide Motifs; Promoter Regions, Genetic; Protein Binding; Protein Domains; Regulon; Siderophores; Surface Plasmon Resonance; Transcription Factors
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