Kwang-Woo Jung^1,*, Dong-Hoon Yang^1,*, Shinae Maeng¹, Kyung-Tae Lee¹, Yee-Seul So¹, Joohyeon Hong², Jaeyoung Choi³, Hyo-Jeong Byun¹, Hyelim Kim¹, Soohyun Bang¹, Min-Hee Song¹, Jang-Won Lee¹, Min Su Kim¹, Seo-Young Kim¹, Je-Hyun Ji¹, Goun Park¹, Hyojeong Kwon¹, Suyeon Cha¹, Gena Lee Meyers¹, Li Li Wang¹, Jooyoung Jang¹, Guilhem Janbon⁴, Gloria Adedoyin⁵, Taeyup Kim⁵, Anna K. Averette⁵, Joseph Heitman⁵, Eunji Cheong², Yong-Hwan Lee³, Yin-Won Lee³ & Yong-Sun Bahn¹

¹ Department of Biotechnology, Center for Fungal Pathogenesis, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
² Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea. ³ Department of Agricultural Biotechnology, Center for Fungal Pathogenesis, Seoul National University, Seoul 151-921, Korea. ⁴ Unite Biologie et Pathogenicite Fongiques, Departement de Mycologie, Institut Pasteur, Paris F-75015, France. ⁵ Department of Molecular Genetics and Microbiology, Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. ^* These authors contributed equally to this work.

Correspondence to:  Yong-Sun Bahn

Abstract
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 B85% 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.