Regulatory networks underlying mycorrhizal development delineated by genome-wide expression profiling and functional analysis of the transcription factor repertoire of the plant symbiotic fungus Laccaria bicolor
Abstract
Background: Ectomycorrhizal (ECM) fungi develop a mutualistic symbiotic interaction with the roots of their host plants. During this process, they undergo a series of developmental transitions from the running hyphae in the rhizosphere to the coenocytic hyphae forming finger-like structures within the root apoplastic space. These transitions, which involve profound, symbiosis-associated metabolic changes, also entail a substantial transcriptome reprogramming with coordinated waves of differentially expressed genes. To date, little is known about the key transcriptional regulators driving these changes, and the aim of the present study was to delineate and functionally characterize the transcription factor (TF) repertoire of the model ECM fungus Laccaria bicolor. Results: We curated the L. bicolor gene models coding for transcription factors and assessed their expression and regulation in Poplar and Douglas fir ectomycorrhizae. We identified 285 TFs, 191 of which share a significant similarity with known transcriptional regulators. Expression profiling of the corresponding transcripts identified TF-encoding fungal genes differentially expressed in the ECM root tips of both host plants. The L. bicolor core set of differentially expressed TFs consists of 12 and 22 genes that are, respectively, upregulated and downregulated in symbiotic tissues. These TFs resemble known fungal regulators involved in the control of fungalmore »
- Authors:
-
- Univ. de Lorraine, Champenoux (France). Interactions Arbres/ Microorganismes, Laboratoire d’Excellence ARBRE; Univ. de Lorraine, Nancy (France). Interactions Arbres/Microorganismes, Laboratoire d’Excellence ARBRE
- Univ. degli Studi di Parma (Italy). Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità Ambientale
- Publication Date:
- Research Org.:
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1626809
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Journal Article: Accepted Manuscript
- Journal Name:
- BMC Genomics
- Additional Journal Information:
- Journal Volume: 18; Journal Issue: 1; Journal ID: ISSN 1471-2164
- Publisher:
- Springer
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; Biotechnology & Applied Microbiology; Genetics & Heredity; Transcription factors; symbiosis; secreted proteins; transcriptional activator trap assay; yeast; transcriptome; ectomycorrhiza development
Citation Formats
Daguerre, Y., Levati, E., Ruytinx, J., Tisserant, E., Morin, E., Kohler, A., Montanini, B., Ottonello, S., Brun, A., Veneault-Fourrey, C., and Martin, F. Regulatory networks underlying mycorrhizal development delineated by genome-wide expression profiling and functional analysis of the transcription factor repertoire of the plant symbiotic fungus Laccaria bicolor. United States: N. p., 2017.
Web. doi:10.1186/s12864-017-4114-7.
Daguerre, Y., Levati, E., Ruytinx, J., Tisserant, E., Morin, E., Kohler, A., Montanini, B., Ottonello, S., Brun, A., Veneault-Fourrey, C., & Martin, F. Regulatory networks underlying mycorrhizal development delineated by genome-wide expression profiling and functional analysis of the transcription factor repertoire of the plant symbiotic fungus Laccaria bicolor. United States. https://doi.org/10.1186/s12864-017-4114-7
Daguerre, Y., Levati, E., Ruytinx, J., Tisserant, E., Morin, E., Kohler, A., Montanini, B., Ottonello, S., Brun, A., Veneault-Fourrey, C., and Martin, F. 2017.
"Regulatory networks underlying mycorrhizal development delineated by genome-wide expression profiling and functional analysis of the transcription factor repertoire of the plant symbiotic fungus Laccaria bicolor". United States. https://doi.org/10.1186/s12864-017-4114-7. https://www.osti.gov/servlets/purl/1626809.
@article{osti_1626809,
title = {Regulatory networks underlying mycorrhizal development delineated by genome-wide expression profiling and functional analysis of the transcription factor repertoire of the plant symbiotic fungus Laccaria bicolor},
author = {Daguerre, Y. and Levati, E. and Ruytinx, J. and Tisserant, E. and Morin, E. and Kohler, A. and Montanini, B. and Ottonello, S. and Brun, A. and Veneault-Fourrey, C. and Martin, F.},
abstractNote = {Background: Ectomycorrhizal (ECM) fungi develop a mutualistic symbiotic interaction with the roots of their host plants. During this process, they undergo a series of developmental transitions from the running hyphae in the rhizosphere to the coenocytic hyphae forming finger-like structures within the root apoplastic space. These transitions, which involve profound, symbiosis-associated metabolic changes, also entail a substantial transcriptome reprogramming with coordinated waves of differentially expressed genes. To date, little is known about the key transcriptional regulators driving these changes, and the aim of the present study was to delineate and functionally characterize the transcription factor (TF) repertoire of the model ECM fungus Laccaria bicolor. Results: We curated the L. bicolor gene models coding for transcription factors and assessed their expression and regulation in Poplar and Douglas fir ectomycorrhizae. We identified 285 TFs, 191 of which share a significant similarity with known transcriptional regulators. Expression profiling of the corresponding transcripts identified TF-encoding fungal genes differentially expressed in the ECM root tips of both host plants. The L. bicolor core set of differentially expressed TFs consists of 12 and 22 genes that are, respectively, upregulated and downregulated in symbiotic tissues. These TFs resemble known fungal regulators involved in the control of fungal invasive growth, fungal cell wall integrity, carbon and nitrogen metabolism, invasive stress response and fruiting-body development. However, this core set of mycorrhiza-regulated TFs seems to be characteristic of L. bicolor and our data suggest that each mycorrhizal fungus has evolved its own set of ECM development regulators. A subset of the above TFs was functionally validated with the use of a heterologous, transcription activation assay in yeast, which also allowed the identification of previously unknown, transcriptionally active yet secreted polypeptides designated as Secreted Transcriptional Activator Proteins (STAPs). Conclusions: Transcriptional regulators required for ECM symbiosis development in L. bicolor have been uncovered and classified through genome-wide analysis. This study also identifies the STAPs as a new class of potential ECM effectors, highly expressed in mycorrhizae, which may be involved in the control of the symbiotic root transcriptome.},
doi = {10.1186/s12864-017-4114-7},
url = {https://www.osti.gov/biblio/1626809},
journal = {BMC Genomics},
issn = {1471-2164},
number = 1,
volume = 18,
place = {United States},
year = {Mon Sep 18 00:00:00 EDT 2017},
month = {Mon Sep 18 00:00:00 EDT 2017}
}
Works referenced in this record:
The Mutualist Laccaria bicolor Expresses a Core Gene Regulon During the Colonization of Diverse Host Plants and a Variable Regulon to Counteract Host-Specific Defenses
journal, March 2015
- Plett, Jonathan M.; Tisserant, Emilie; Brun, Annick
- Molecular Plant-Microbe Interactions, Vol. 28, Issue 3
The Ectomycorrhizal Infection zone and its Relation to acid Polysaccharides of Cortical cell Walls
journal, May 1987
- Nylund, Jan-Erik
- New Phytologist, Vol. 106, Issue 1
Transcription factor genes of Schizophyllum commune involved in regulation of mushroom formation: Regulation of mushroom formation
journal, August 2011
- Ohm, Robin A.; de Jong, Jan F.; de Bekker, Charissa
- Molecular Microbiology, Vol. 81, Issue 6
The genome of Laccaria bicolor provides insights into mycorrhizal symbiosis
journal, March 2008
- Martin, F.; Aerts, A.; Ahrén, D.
- Nature, Vol. 452, Issue 7183
Yeast RLM1 encodes a serum response factor-like protein that may function downstream of the Mpk1 (Slt2) mitogen-activated protein kinase pathway.
journal, October 1995
- Watanabe, Y.; Irie, K.; Matsumoto, K.
- Molecular and Cellular Biology, Vol. 15, Issue 10
Insights into evolution of multicellular fungi from the assembled chromosomes of the mushroom Coprinopsis cinerea (Coprinus cinereus)
journal, June 2010
- Stajich, J. E.; Wilke, S. K.; Ahren, D.
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 26
Profiling the Human Protein-DNA Interactome Reveals ERK2 as a Transcriptional Repressor of Interferon Signaling
journal, October 2009
- Hu, Shaohui; Xie, Zhi; Onishi, Akishi
- Cell, Vol. 139, Issue 3
Transcriptional activators in yeast
journal, February 2006
- Titz, B.
- Nucleic Acids Research, Vol. 34, Issue 3
Mating in mushrooms: increasing the chances but prolonging the affair
journal, July 2001
- Brown, A.
- Trends in Genetics, Vol. 17, Issue 7
The acetate regulatory gene facB of Aspergillus nidulans encodes a Zn(II)2Cys6 transcriptional activator
journal, May 1997
- Todd, R. B.; Murphy, R. L.; Martin, H. M.
- Molecular and General Genetics MGG, Vol. 254, Issue 5
H2O2 sensing through oxidation of the Yap1 transcription factor
journal, October 2000
- Delaunay, Agnès; Isnard, Anne-Dominique; Toledano, Michel B.
- The EMBO Journal, Vol. 19, Issue 19
Activation of an AP1-Like Transcription Factor of the Maize Pathogen Cochliobolus heterostrophus in Response to Oxidative Stress and Plant Signals
journal, February 2005
- Lev, Sophie; Hadar, Ruthi; Amedeo, Paolo
- Eukaryotic Cell, Vol. 4, Issue 2
Genome-wide search and functional identification of transcription factors in the mycorrhizal fungus Tuber melanosporum
journal, November 2010
- Montanini, Barbara; Levati, Elisabetta; Bolchi, Angelo
- New Phytologist, Vol. 189, Issue 3
Metabolic enzymes and coenzymes in transcription – a direct link between metabolism and transcription?
journal, September 2004
- Shi, Yujiang; Shi, Yang
- Trends in Genetics, Vol. 20, Issue 9
MADS-Box Transcription Factor Mig1 Is Required for Infectious Growth in Magnaporthe grisea
journal, March 2008
- Mehrabi, Rahim; Ding, Shengli; Xu, Jin-Rong
- Eukaryotic Cell, Vol. 7, Issue 5
Mycorrhizal ecology and evolution: the past, the present, and the future
journal, February 2015
- van der Heijden, Marcel G. A.; Martin, Francis M.; Selosse, Marc-André
- New Phytologist, Vol. 205, Issue 4
Phylogenetic, genomic organization and expression analysis of hydrophobin genes in the ectomycorrhizal basidiomycete Laccaria bicolor
journal, March 2012
- Plett, Jonathan M.; Gibon, Julien; Kohler, Annegret
- Fungal Genetics and Biology, Vol. 49, Issue 3
The Aspergillus nidulans abaA gene encodes a transcriptional activator that acts as a genetic switch to control development.
journal, April 1994
- Andrianopoulos, A.; Timberlake, W. E.
- Molecular and Cellular Biology, Vol. 14, Issue 4
Dry and wet approaches for genome-wide functional annotation of conventional and unconventional transcriptional activators
journal, January 2016
- Levati, Elisabetta; Sartini, Sara; Ottonello, Simone
- Computational and Structural Biotechnology Journal, Vol. 14
Moonlighting transcriptional activation function of a fungal sulfur metabolism enzyme
journal, April 2016
- Levati, Elisabetta; Sartini, Sara; Bolchi, Angelo
- Scientific Reports, Vol. 6, Issue 1
Ontogeny of Alnus rubra – Alpova diplophloeus ectomycorrhizae. I. Light microscopy and scanning electron microscopy
journal, January 1989
- Massicotte, H. B.; Peterson, R. L.; Melville, L. H.
- Canadian Journal of Botany, Vol. 67, Issue 1
A Secreted Effector Protein of Laccaria bicolor Is Required for Symbiosis Development
journal, July 2011
- Plett, Jonathan M.; Kemppainen, Minna; Kale, Shiv D.
- Current Biology, Vol. 21, Issue 14
Périgord black truffle genome uncovers evolutionary origins and mechanisms of symbiosis
journal, March 2010
- Martin, Francis; Kohler, Annegret; Murat, Claude
- Nature, Vol. 464, Issue 7291
Prevalence of transcription factors in ascomycete and basidiomycete fungi
journal, January 2014
- Todd, Richard B.; Zhou, Miaomiao; Ohm, Robin A.
- BMC Genomics, Vol. 15, Issue 1
Ectomycorrhizal ecology is imprinted in the genome of the dominant symbiotic fungus Cenococcum geophilum
journal, September 2016
- Peter, Martina; Kohler, Annegret; Ohm, Robin A.
- Nature Communications, Vol. 7, Issue 1
Coevolution of roots and mycorrhizas of land plants
journal, May 2002
- Brundrett, Mark C.
- New Phytologist, Vol. 154, Issue 2
The pheromone response factor coordinates filamentous growth and pathogenicity in Ustilago maydis.
journal, April 1996
- Hartmann, H. A.; Kahmann, R.; Bölker, M.
- The EMBO Journal, Vol. 15, Issue 7
CreA influences the metabolic fluxes of Aspergillus nidulans during growth on glucose and xylose
journal, July 2005
- David, H.
- Microbiology, Vol. 151, Issue 7
Rfg1, a Protein Related to the Saccharomyces cerevisiae Hypoxic Regulator Rox1, Controls Filamentous Growth and Virulence in Candida albicans
journal, April 2001
- Kadosh, David; Johnson, Alexander D.
- Molecular and Cellular Biology, Vol. 21, Issue 7
MpkA-Dependent and -Independent Cell Wall Integrity Signaling in Aspergillus nidulans
journal, June 2007
- Fujioka, Tomonori; Mizutani, Osamu; Furukawa, Kentaro
- Eukaryotic Cell, Vol. 6, Issue 8
Regulation of the yeast Rlm1 transcription factor by the Mpk1 cell wall integrity MAP kinase: Reporters for cell wall integrity signalling
journal, October 2002
- Jung, Un Sung; Sobering, Andrew K.; Romeo, Martin J.
- Molecular Microbiology, Vol. 46, Issue 3
A new mathematical model for relative quantification in real-time RT-PCR
journal, May 2001
- Pfaffl, M. W.
- Nucleic Acids Research, Vol. 29, Issue 9
FAR1 and FAR2 Regulate the Expression of Genes Associated with Lipid Metabolism in the Rice Blast Fungus Magnaporthe oryzae
journal, June 2014
- bin Yusof, Mohammad Termizi; Kershaw, Michael J.; Soanes, Darren M.
- PLoS ONE, Vol. 9, Issue 6
Lateral root stimulation in the early interaction between Arabidopsis thaliana and the ectomycorrhizal fungus Laccaria bicolor : Is fungal auxin the trigger?
journal, July 2010
- Felten, Judith; Legué, Valérie; Anicet Ditengou, Franck
- Plant Signaling & Behavior, Vol. 5, Issue 7
A regulator gene for acetate utilisation from Neurospora crassa
journal, June 2002
- Bibbins, M.; Crepin, V.; Cummings, N.
- Molecular Genetics and Genomics, Vol. 267, Issue 4
Spatial patterns of gene expression in the extramatrical mycelium and mycorrhizal root tips formed by the ectomycorrhizal fungus Paxillus involutus in association with birch (Betula pendula) seedlings in soil microcosms
journal, April 2005
- Wright, Derek P.; Johansson, Tomas; Le Quéré, Antoine
- New Phytologist, Vol. 167, Issue 2
Pseudohyphal Regulation by the Transcription Factor Rfg1p in Candida albicans
journal, July 2010
- Cleary, Ian A.; Mulabagal, Priyadarshini; Reinhard, Sara M.
- Eukaryotic Cell, Vol. 9, Issue 9
Effector MiSSP7 of the mutualistic fungus Laccaria bicolor stabilizes the Populus JAZ6 protein and represses jasmonic acid (JA) responsive genes
journal, May 2014
- Plett, J. M.; Daguerre, Y.; Wittulsky, S.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 22
Modification of the Host-Fungus Interface in Mycorrhizas Synthesized Between Suillus Bovjnus (Fr.) o. Kuntz and Pinus Sylvestris l.
journal, April 1984
- Duddridge, J. A.; Read, D. J.
- New Phytologist, Vol. 96, Issue 4
Comparative genomics and expression levels of hydrophobins from eight mycorrhizal genomes
journal, January 2017
- Rineau, F.; Lmalem, H.; Ahren, D.
- Mycorrhiza, Vol. 27, Issue 4
The major pathways of carbohydrate metabolism in the ectomycorrhizal basidiomycete Laccaria bicolor S238N
journal, October 2008
- Deveau, A.; Kohler, A.; Frey-Klett, P.
- New Phytologist, Vol. 180, Issue 2
Convergent losses of decay mechanisms and rapid turnover of symbiosis genes in mycorrhizal mutualists
journal, February 2015
- Kohler, Annegret; Kuo, Alan; Nagy, Laszlo G.
- Nature Genetics, Vol. 47, Issue 4
Genomic and transcriptomic analysis of Laccaria bicolor CAZome reveals insights into polysaccharides remodelling during symbiosis establishment
journal, November 2014
- Veneault-Fourrey, Claire; Commun, Carine; Kohler, Annegret
- Fungal Genetics and Biology, Vol. 72
Regulatory roles for the homeodomain and C2H2 zinc finger regions of Cryptococcus neoformans Ste12αp: Roles of the homeodomain and C2H2 zinc fingers of Ste12απ
journal, August 2004
- Chang, Yun C.; Tscharke, R. L.; Sorrell, T. C.
- Molecular Microbiology, Vol. 53, Issue 5
The Ectomycorrhizal Fungus Laccaria bicolor Stimulates Lateral Root Formation in Poplar and Arabidopsis through Auxin Transport and Signaling
journal, October 2009
- Felten, Judith; Kohler, Annegret; Morin, Emmanuelle
- Plant Physiology, Vol. 151, Issue 4
Transcriptional Responses of Paxillus involutus and Betula pendula During Formation of Ectomycorrhizal Root Tissue
journal, February 2004
- Johansson, Tomas; Le Quéré, Antoine; Ahren, Dag
- Molecular Plant-Microbe Interactions, Vol. 17, Issue 2
Gcn4 co-ordinates morphogenetic and metabolic responses to amino acid starvation in Candida albicans
journal, October 2002
- Tripathi, G.
- The EMBO Journal, Vol. 21, Issue 20
Global Patterns of Gene Regulation Associated with the Development of Ectomycorrhiza Between Birch ( Betula pendula Roth.) and Paxillus involutus (Batsch) Fr.
journal, July 2005
- Le Quéré, Antoine; Wright, Derek P.; Söderström, Bengt
- Molecular Plant-Microbe Interactions, Vol. 18, Issue 7
Variation in mycorrhizal development and growth stimulation by 20 Pisolithus isolates inoculated on to Eucalyptus grandis W. Hill ex Maiden
journal, August 1994
- Burgess, T.; Dell, B.; Malajczuk, N.
- New Phytologist, Vol. 127, Issue 4
Transcript patterns associated with ectomycorrhiza development in Eucalyptus globulus and Pisolithus microcarpus
journal, November 2004
- Duplessis, Sébastien; Courty, Pierre-Emmanuel; Tagu, Denis
- New Phytologist, Vol. 165, Issue 2
Mycorrhizas and nutrient cycling in ecosystems - a journey towards relevance?
journal, March 2003
- Read, D. J.; Perez-Moreno, J.
- New Phytologist, Vol. 157, Issue 3
NAC transcription factors: structurally distinct, functionally diverse
journal, February 2005
- Olsen, Addie Nina; Ernst, Heidi A.; Leggio, Leila Lo
- Trends in Plant Science, Vol. 10, Issue 2
Development of the Poplar -Laccaria bicolor Ectomycorrhiza Modifies Root Auxin Metabolism, Signaling, and Response
journal, June 2015
- Vayssières, Alice; Pěnčík, Ales; Felten, Judith
- Plant Physiology, Vol. 169, Issue 1
Moc3, a novel Zn finger type protein involved in sexual development, ascus formation, and stress response of Schizosaccharomyces pombe
journal, November 2005
- Goldar, M. Muniruzzaman; Jeong, Hee Tae; Tanaka, Katsunori
- Current Genetics, Vol. 48, Issue 6
Structure and ontogeny of Betula alleghaniensis – Pisolithus tinctorius ectomycorrhizae
journal, March 1990
- Massicotte, H. B.; Peterson, R. L.; Ackerley, C. A.
- Canadian Journal of Botany, Vol. 68, Issue 3
Ontogeny of Eucalyptus pilularis – Pisolithus tinctorius ectomycorrhizae. I. Light microscopy and scanning electron microscopy
journal, September 1987
- Massicotte, H. B.; Peterson, R. L.; Ashford, A. E.
- Canadian Journal of Botany, Vol. 65, Issue 9
The MADS-Box transcription factor Bcmads1 is required for growth, sclerotia production and pathogenicity of Botrytis cinerea
journal, September 2016
- Zhang, Zhanquan; Li, Hua; Qin, Guozheng
- Scientific Reports, Vol. 6, Issue 1
Ontogeny of Eucalyptus pilularis – Pisolithus tinctorius ectomycorrhizae. II. Transmission electron microscopy
journal, September 1987
- Massicotte, H. B.; Peterson, R. L.; Ackerley, C. A.
- Canadian Journal of Botany, Vol. 65, Issue 9
The ectomycorrhizal basidiomycete Hebeloma cylindrosporum undergoes early waves of transcriptional reprogramming prior to symbiotic structures differentiation: Hebeloma cylindrosporum pre-infectious transcriptome
journal, February 2017
- Doré, Jeanne; Kohler, Annegret; Dubost, Audrey
- Environmental Microbiology, Vol. 19, Issue 3
Using next generation transcriptome sequencing to predict an ectomycorrhizal metabolome
journal, January 2011
- Larsen, Peter E.; Sreedasyam, Avinash; Trivedi, Geetika
- BMC Systems Biology, Vol. 5, Issue 1
Regulation of Gene Expression by a Metabolic Enzyme
journal, October 2004
- Hall, D. A.
- Science, Vol. 306, Issue 5695
Structure and ontogeny of Alnus crispa – Alpova diplophloeus ectomycorrhizae
journal, January 1986
- Massicotte, H. B.; Peterson, R. L.; Ackerley, C. A.
- Canadian Journal of Botany, Vol. 64, Issue 1
The R2R3-MYB gene family in Arabidopsis thaliana
journal, October 2001
- Stracke, Ralf; Werber, Martin; Weisshaar, Bernd
- Current Opinion in Plant Biology, Vol. 4, Issue 5, p. 447-456
Ste12 and Ste12-Like Proteins, Fungal Transcription Factors Regulating Development and Pathogenicity
journal, February 2010
- Wong Sak Hoi, Joanne; Dumas, Bernard
- Eukaryotic Cell, Vol. 9, Issue 4
Comparative structure of vesicular-arbuscular mycorrhizas and ectomycorrhizas
journal, February 1994
- Peterson, R. Larry; Bonfante, Paola
- Plant and Soil, Vol. 159, Issue 1
Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus
journal, July 2015
- Shin, Kwang-Soo; Kim, Young Hwan; Yu, Jae-Hyuk
- Biochemical and Biophysical Research Communications, Vol. 463, Issue 3
Laser Capture Microdissection of Uredinia Formed by Melampsora larici-populina Revealed a Transcriptional Switch Between Biotrophy and Sporulation
journal, October 2010
- Hacquard, Stéphane; Delaruelle, Christine; Legué, Valérie
- Molecular Plant-Microbe Interactions®, Vol. 23, Issue 10
Unearthing the roots of ectomycorrhizal symbioses
journal, October 2016
- Martin, Francis; Kohler, Annegret; Murat, Claude
- Nature Reviews Microbiology, Vol. 14, Issue 12
The Ectomycorrhizal Infection zone and its Relation to acid Polysaccharides of Cortical cell Walls
journal, July 1987
- Nylund, Jan-Erik
- New Phytologist, Vol. 106, Issue 3
Integrated analyses of the transcriptome and small RNA of the hemiparasitic plant Monochasma savatieri before and after establishment of parasite-host association
journal, February 2021
- Chen, Lanlan; Guo, Qiaosheng; Zhu, Zaibiao
- BMC Plant Biology, Vol. 21, Issue 1
The Aspergillus nidulans abaA gene encodes a transcriptional activator that acts as a genetic switch to control development
journal, April 1994
- Andrianopoulos, A.; Timberlake, W. E.
- Molecular and Cellular Biology, Vol. 14, Issue 4