Systematic functional profiling of transcription factor networks in Cryptococcus neoformans

Kwang Woo Jung, Dong Hoon Yang, Shinae Maeng, Kyung Tae Lee, Yee Seul So, Joohyeon Hong, Jaeyoung Choi, Hyo Jeong Byun, Hyelim Kim, Soohyun Bang, Min Hee Song, Jang Won Lee, Min Su Kim, Seo Young Kim, Je Hyun Ji, Goun Park, Hyojeong Kwon, Suyeon Cha, Gena Lee Meyers, Li Li WangJooyoung Jang, Guilhem Janbon, Gloria Adedoyin, Taeyup Kim, Anna K. Averette, Joseph Heitman, Eunji Cheong, Yong Hwan Lee, Yin Won Lee, Yong Sun Bahn

Research output: Contribution to journalArticle

60 Citations (Scopus)

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 ∼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.

Original languageEnglish
Article number6757
JournalNature communications
Volume6
DOIs
Publication statusPublished - 2015 Apr 13

Fingerprint

Cryptococcus neoformans
Transcription Factors
genes
Genes
Databases
functional analysis
deletion
Functional analysis
Meningoencephalitis
pathogens
fungi
Gene Regulatory Networks
Gene Deletion
Pathogens
Fungi
Libraries
deoxyribonucleic acid
signatures
Networks (circuits)
causes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Jung, Kwang Woo ; Yang, Dong Hoon ; Maeng, Shinae ; Lee, Kyung Tae ; So, Yee Seul ; Hong, Joohyeon ; Choi, Jaeyoung ; Byun, Hyo Jeong ; Kim, Hyelim ; Bang, Soohyun ; Song, Min Hee ; Lee, Jang Won ; Kim, Min Su ; Kim, Seo Young ; Ji, Je Hyun ; Park, Goun ; Kwon, Hyojeong ; Cha, Suyeon ; Meyers, Gena Lee ; Wang, Li Li ; Jang, Jooyoung ; Janbon, Guilhem ; Adedoyin, Gloria ; Kim, Taeyup ; Averette, Anna K. ; Heitman, Joseph ; Cheong, Eunji ; Lee, Yong Hwan ; Lee, Yin Won ; Bahn, Yong Sun. / Systematic functional profiling of transcription factor networks in Cryptococcus neoformans. In: Nature communications. 2015 ; Vol. 6.
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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 ∼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.",
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Jung, KW, Yang, DH, Maeng, S, Lee, KT, So, YS, Hong, J, Choi, J, Byun, HJ, Kim, H, Bang, S, Song, MH, Lee, JW, Kim, MS, Kim, SY, Ji, JH, Park, G, Kwon, H, Cha, S, Meyers, GL, Wang, LL, Jang, J, Janbon, G, Adedoyin, G, Kim, T, Averette, AK, Heitman, J, Cheong, E, Lee, YH, Lee, YW & Bahn, YS 2015, 'Systematic functional profiling of transcription factor networks in Cryptococcus neoformans', Nature communications, vol. 6, 6757. https://doi.org/10.1038/ncomms7757

Systematic functional profiling of transcription factor networks in Cryptococcus neoformans. / Jung, Kwang Woo; Yang, Dong Hoon; Maeng, Shinae; Lee, Kyung Tae; So, Yee Seul; Hong, Joohyeon; Choi, Jaeyoung; Byun, Hyo Jeong; Kim, Hyelim; Bang, Soohyun; Song, Min Hee; Lee, Jang Won; Kim, Min Su; Kim, Seo Young; Ji, Je Hyun; Park, Goun; Kwon, Hyojeong; Cha, Suyeon; Meyers, Gena Lee; Wang, Li Li; Jang, Jooyoung; Janbon, Guilhem; Adedoyin, Gloria; Kim, Taeyup; Averette, Anna K.; Heitman, Joseph; Cheong, Eunji; Lee, Yong Hwan; Lee, Yin Won; Bahn, Yong Sun.

In: Nature communications, Vol. 6, 6757, 13.04.2015.

Research output: Contribution to journalArticle

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AU - Jung, Kwang Woo

AU - Yang, Dong Hoon

AU - Maeng, Shinae

AU - Lee, Kyung Tae

AU - So, Yee Seul

AU - Hong, Joohyeon

AU - Choi, Jaeyoung

AU - Byun, Hyo Jeong

AU - Kim, Hyelim

AU - Bang, Soohyun

AU - Song, Min Hee

AU - Lee, Jang Won

AU - Kim, Min Su

AU - Kim, Seo Young

AU - Ji, Je Hyun

AU - Park, Goun

AU - Kwon, Hyojeong

AU - Cha, Suyeon

AU - Meyers, Gena Lee

AU - Wang, Li Li

AU - Jang, Jooyoung

AU - Janbon, Guilhem

AU - Adedoyin, Gloria

AU - Kim, Taeyup

AU - Averette, Anna K.

AU - Heitman, Joseph

AU - Cheong, Eunji

AU - Lee, Yong Hwan

AU - Lee, Yin Won

AU - Bahn, Yong Sun

PY - 2015/4/13

Y1 - 2015/4/13

N2 - 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.

AB - 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.

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