Cryptococcus neoformans causes life-threatening meningoencephalitis in humans, but its overall biological and pathogenic regulatory circuits remain elusive, particularly due to the presence of an evolutionarily divergent set of transcription factors (TFs). Here, we report the construction of a high-quality library of 322 signature-tagged gene-deletion strains for 155 putative TF genes previously predicted using the DNA-binding domain TF database, and examine their in vitro and in vivo phenotypic traits under 32 distinct growth conditions. At least one phenotypic trait is exhibited by 145 out of 155 TF mutants (93%) and ∼85% of them (132/155) are functionally characterized for the first time in this study. The genotypic and phenotypic data for each TF are available in the C. neoformans TF phenome database (http://tf.cryptococcus.org). In conclusion, our phenome-based functional analysis of the C. neoformans TF mutant library provides key insights into transcriptional networks of basidiomycetous fungi and human fungal pathogens.
Bibliographical noteFunding Information:
We thank Hanna Na, Moonyoung Park, Yongjae Song, Yooyeon Kim, Kyeongseon Ryu, Changho Lee, Ja-Kyung Yoon, Seung-Yeol Lee, Heejung Ahn, Jihwan Lee, Hyunsoo Kim and Sunghyun Kim for their technical assistance in constructing the TF mutant library. This work was supported by National Research Foundation of Korea grants (nos 2008-0061963 and 2010-0029117) from MEST (to Y.-S.B.). This work was also supported in part by NIH/NIAID R01-AI050438-10 to J.H. and ANR (2010-BLAN-1620-01 program YeastIntrons) to G.J.
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)