The cold-induced transcription factor bHLH112 promotes artemisinin biosynthesis indirectly via ERF1 in Artemisia annua
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Basic helix-loop-helix (bHLH) proteins are the second largest family of transcription factors (TFs) involved in developmental and physiological processes in plants. In this study, 205 putative bHLH TF genes were identified in the genome of Artemisia annua and expression of 122 of these was determined from transcriptomes used to construct the genetic map of A. annua. Analysis of gene expression association allowed division of the 122 bHLH TFs into five groups. Group V, containing 15 members, was tightly associated with artemisinin biosynthesis genes. Phylogenetic analysis indicated that two bHLH TFs, AabHLH106 and AabHLH112, were clustered with Arabidopsis ICE proteins. AabHLH112 was induced by low temperature, while AabHLH106 was not. We therefore chose AabHLH112 for further examination. AabHLH112 was highly expressed in glandular secretory trichomes, flower buds, and leaves. Dual-luciferase assays demonstrated that AabHLH112 enhanced the promoter activity of artemisinin biosynthesis genes and AaERF1, an AP2/ERF TF that directly and positively regulates artemisinin biosynthesis genes. Yeast one-hybrid assays indicated that AabHLH112 could bind to the AaERF1 promoter, but not to the promoters of artemisinin biosynthesis genes. Overexpression of AabHLH112 significantly up-regulated the expression levels of AaERF1 and artemisinin biosynthesis genes and consequently promoted artemisinin production.
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Various environmental stresses like heavy metal pollution, cold, water (drought and flooding), light, pest and disease damage affect accumulation of specialty metabolites in plants including artemisinin in A. annua.
“Besides elicitors and plant growth regulators, various environmental stresses like heavy metal pollution, cold, water (drought and flooding), light, pest and disease damage affect accumulation of specialty metabolites in plants including artemisinin in A. annua (Xiang et al. 2019; Hao et al. 2019; Soni and Abdin 2017; Yin et al. 2008).”
From Enhancing artemisinin content in and delivery from Artemisia annua: a review of alternative, classical, and transgenic approaches (2021) · cites this paper as Xiang et al. 2019
The Introduction (page not provided) says that temperature, water, and light affect secondary-metabolite biosynthesis, including artemisinin, and specifically describes increased artemisinin production under cold conditions. It does not address heavy-metal pollution, flooding, or pest and disease damage; the cited reference to water deficit supports drought only indirectly. (LLM, conf=0.86)
Experimental — accuracy not yet measuredExpression of these genes occurs in a coordinated manner under low temperature, hinting at participation of specific transcription factors in regulating artemisinin biosynthesis under such conditions.
“Expression of these genes occurs in a coordinated manner under low temperature, hinting at the participation of certain specific transcription factors in regulating artemisinin biosynthesis under such conditions (Xiang et al. 2019).”
From Enhancing artemisinin content in and delivery from Artemisia annua: a review of alternative, classical, and transgenic approaches (2021) · cites this paper as Xiang et al. 2019
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Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Thompson, J. D., Higgins, D. G., & Gibson, T. J. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.22.4673 · Cited by 64,617 · see citing works
FastTree: Computing Large Minimum Evolution Trees with Profiles instead of a Distance Matrix
Price, M. N., Dehal, P. S., & Arkin, A. P. (2009) · Molecular Biology and Evolution · doi:10.1093/molbev/msp077 · Cited by 5,602 · see citing works
MYB transcription factors in Arabidopsis
Dubos, C., Stracke, R., Erich Grotewold, A., Weißhaar, B., Martin, C. R., & Lepiniec, L. (2010) · Trends in Plant Science · doi:10.1016/j.tplants.2010.06.005 · Cited by 4,885 · see citing works
NCBI BLAST: a better web interface
Johnson, M., Zaretskaya, I., Raytselis, Y., Merezhuk, Y., McGinnis, S., & Madden, T. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn201 · Cited by 4,207 · see citing works
Plant cis-acting regulatory DNA elements (PLACE) database: 1999
Higo, K., Ugawa, Y., Iwamoto, M., & Korenaga, T. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.1.297 · Cited by 3,387 · see citing works
bZIP transcription factors in Arabidopsis
Jakoby, M. J., Weißhaar, B., Dröge‐Laser, W., Vicente‐Carbajosa, J., Tiedemann, J., Kroj, T., & Parcy, F. (2002) · Trends in Plant Science · doi:10.1016/s1360-1385(01)02223-3 · Cited by 1,862 · see citing works
ICE1: a regulator of cold-induced transcriptome and freezing tolerance in ArabidopsisPreprint
Chinnusamy, V., Ohta, M., Kanrar, S., Lee, B., Hong, X., Agarwal, M., & Zhu, J. (2003) · Genes & Development · doi:10.1101/gad.1077503 · Cited by 1,669 · see citing works
The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine
Tu, Y. (2011) · Nature Medicine · doi:10.1038/nm.2471 · Cited by 1,397 · see citing works
Heim, M. A. (2003) · Molecular Biology and Evolution · doi:10.1093/molbev/msg088 · Cited by 1,056 · see citing works
Qinghaosu (Artemisinin): The Price of Success
White, N. J. (2008) · Science · doi:10.1126/science.1155165 · Cited by 954 · see citing works
Hu, Y., Jiang, L., Wang, F., & Yu, D. (2013) · The Plant Cell · doi:10.1105/tpc.113.112631 · Cited by 830 · see citing works
Payne, C. T., Zhang, F., & Lloyd, A. (2000) · Genetics · doi:10.1093/genetics/156.3.1349 · Cited by 766 · see citing works
Self-citationXie, X., LI, S., Zhang, R., ZHAO, J., CHEN, Y., Zhao, Q., YAO, Y., You, C., ZHANG, X., & Hao, Y. (2012) · Plant Cell & Environment · doi:10.1111/j.1365-3040.2012.02523.x · Cited by 750 · see citing works
Genome-Wide Analysis of Basic/Helix-Loop-Helix Transcription Factor Family in Rice and Arabidopsis
Li, X., Duan, X., Jiang, H., Sun, Y., Tang, Y., Yuan, Z., Guo, J., Liang, W., Chen, L., Yin, J., et al. (2006) · PLANT PHYSIOLOGY · doi:10.1104/pp.106.080580 · Cited by 697 · see citing works
Arabidopsis MYC2 Interacts with DELLA Proteins in Regulating Sesquiterpene Synthase Gene Expression
Hong, G., Xue, X., Mao, Y., Wang, L.-J., & Chen, X. (2012) · The Plant Cell · doi:10.1105/tpc.112.098749 · Cited by 683 · see citing works
Carretero‐Paulet, L., Galstyan, A., Roig‐Villanova, I., Martínez‐García, J. F., Bilbao-Castro, J. R., & Robertson, D. L. (2010) · PLANT PHYSIOLOGY · doi:10.1104/pp.110.153593 · Cited by 681 · see citing works
Artemisinin-Based Combination Treatment of Falciparum Malaria
Nosten, F. H., & White, N. J. (2007) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2007.77.181 · Cited by 663 · see citing works
Ludwig, S. R., Habera, L. F., Dellaporta, S. L., & Wessler, S. R. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.18.7092 · Cited by 614 · see citing works
Schaart, J. G., Dubos, C., Fuente, I. R. D. L., et al. (2012) · New Phytologist · doi:10.1111/nph.12017 · Cited by 556 · see citing works
Plant hormone signaling lightens up: integrators of light and hormones
Lau, O. S., & Deng, X. W. (2010) · Current Opinion in Plant Biology · doi:10.1016/j.pbi.2010.07.001 · Cited by 492 · see citing works
Yu, Z.-X., Li, J., Yang, C., Hu, W., Wang, L.-J., & Chen, X. (2011) · Molecular Plant · doi:10.1093/mp/ssr087 · Cited by 474 · see citing works
Self-citationTeoh, K. H., Polichuk, D. R., Reed, D. W., Nowak, G., & Covello, P. S. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.01.065 · Cited by 409 · see citing works
Jasmonate-responsive transcription factors regulating plant secondary metabolism
Zhou, M., & Memelink, J. (2016) · Biotechnology Advances · doi:10.1016/j.biotechadv.2016.02.004 · Cited by 378 · see citing works
Graham, I. A., Besser, K., Blumer, S., Branigan, C. A., Czechowski, T., Elias, L., Guterman, I., Harvey, D., Isaac, P. G., Khan, A. M., et al. (2010) · Science · doi:10.1126/science.1182612 · Cited by 348 · see citing works
Transcription factors controlling plant secondary metabolism: what regulates the regulators?
Endt, D. V. (2002) · Phytochemistry · doi:10.1016/s0031-9422(02)00185-1 · Cited by 333 · see citing works
Zhang, Y., Teoh, K. H., Reed, D. W., Maes, L., Goossens, A., Olson, D. J. H., Ross, A. R. S., & Covello, P. S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803090200 · Cited by 312 · see citing works
Shen, Q., Zhang, L., Liao, Z., Wang, S., Yan, T., Shi, P., Liu, M., Fu, X., Pan, Q., Wang, Y., et al. (2018) · Molecular Plant · doi:10.1016/j.molp.2018.03.015 · Cited by 312 · see citing works
Self-citationLu, X., Zhang, L., Zhang, F., Jiang, W., Shen, Q., Zhang, L., Lv, Z., Wang, G., & Tang, K. (2013) · New Phytologist · doi:10.1111/nph.12207 · Cited by 299 · see citing works
Self-citationShen, Q., Lu, X., Yan, T., Fu, X., Lv, Z., Zhang, F., Pan, Q., Wang, G., Sun, X., & Tang, K. (2016) · New Phytologist · doi:10.1111/nph.13874 · Cited by 296 · see citing works
Self-citationWallaart, T. E., Pras*, N., Beekman, A., & Quax, W. J. (2000) · Planta Medica · doi:10.1055/s-2000-11115 · Cited by 281 · see citing works
Fursova, O. V., Pogorelko, G. V., & Tarasov, V. A. (2009) · Gene · doi:10.1016/j.gene.2008.10.016 · Cited by 276 · see citing works
Teoh, K. H., Polichuk, D. R., Reed, D. W., & Covello, P. S. (2009) · Botany · doi:10.1139/b09-032 · Cited by 251 · see citing works
Zhang, F., Fu, X., Lv, Z., Lu, X., Shen, Q., Zhang, L., Zhu, M., Wang, G., Sun, X., Liao, Z., et al. (2015) · Molecular Plant · doi:10.1016/j.molp.2014.12.004 · Cited by 248 · see citing works
Self-citationMaes, L., Van Nieuwerburgh, F. C. W., Zhang, Y., Reed, D. W., Pollier, J., Vande Casteele, S. R. F., Inzé, D., Covello, P. S., Deforce, D. L. D., & Goossens, A. (2011) · New Phytologist · doi:10.1111/j.1469-8137.2010.03466.x · Cited by 240 · see citing works
GLANDULAR TRICHOME ‐ SPECIFIC WRKY 1 promotes artemisinin biosynthesis in Artemisia annua
Chen, M., Yan, T., Shen, Q., Lu, X., Pan, Q., Huang, Y., Tang, Y., Fu, X., Liu, M., Jiang, W., et al. (2016) · New Phytologist · doi:10.1111/nph.14373 · Cited by 230 · see citing works
Self-citationMoerkercke, A. V., Steensma, P., Schweizer, F., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1504951112 · Cited by 227 · see citing works
Global characterization of Artemisia annua glandular trichome transcriptome using 454 pyrosequencing
Wang, W., Wang, Y., Zhang, Q., Qi, Y., & Guo, D. (2009) · BMC Genomics · doi:10.1186/1471-2164-10-465 · Cited by 224 · see citing works
Participation of the Arabidopsis bHLH Factor GL3 in Trichome Initiation Regulatory Events
Morohashi, K., Zhao, M., Yang, M., et al. (2007) · PLANT PHYSIOLOGY · doi:10.1104/pp.107.104521 · Cited by 221 · see citing works
Schulz, E., Tohge, T., Zuther, E., et al. (2015) · Plant Cell & Environment · doi:10.1111/pce.12518 · Cited by 212 · see citing works
Zhang, L., Jing, F., Li, F., Li, M., Wang, Y., Wang, G., Sun, X., & Tang, K. (2009) · Biotechnology and Applied Biochemistry · doi:10.1042/ba20080068 · Cited by 206 · see citing works
Self-citationGenome-Wide Identification and Characterization of the Potato bHLH Transcription Factor Family
Wang, R., Zhao, P., Kong, N., Lu, R., Pei, Y., Huang, C., Ma, H., & Chen, Q. (2018) · Genes · doi:10.3390/genes9010054 · Cited by 184 · see citing works
Tan, H., Ling Zhi, X. I. A. O., Gao, S., Li, Q., Chen, J., Xiao, Y., Ji, Q., Chen, R., Chen, W., & Zhang, L. (2015) · Molecular Plant · doi:10.1016/j.molp.2015.04.002 · Cited by 178 · see citing works
Ji, Y., Xiao, J., Shen, Y., Ma, D., Li, Z., Pu, G., Li, X., Huang, L., Liu, B., Ye, H., et al. (2014) · Plant and Cell Physiology · doi:10.1093/pcp/pcu090 · Cited by 171 · see citing works
Jasmonate promotes artemisinin biosynthesis by activating the TCP14-ORA complex in Artemisia annua
Ma, Y., Xu, D.-B., Li, L., Zhang, F., Fu, X., Shen, Q., Lyu, X.-Y., Wu, Z., Pan, Q., Shi, P., et al. (2018) · Science Advances · doi:10.1126/sciadv.aas9357 · Cited by 165 · see citing works
Self-citationStructure and Functional Analysis of Wheat ICE (Inducer of CBF Expression) Genes
Badawi, M., Reddy, Y. V., Agharbaoui, Z., Tominaga, Y., Danyluk, J., Sarhan, F., & Houde, M. (2008) · Plant and Cell Physiology · doi:10.1093/pcp/pcn100 · Cited by 151 · see citing works
Jiménez‐Guerrero, I., Acosta‐Jurado, S., del Cerro, P., Navarro‐Gómez, P., López‐Baena, F. J., Ollero, F. J., Vinardell, J., & Pérez‐Montaño, F. (2017) · Genes · doi:10.3390/genes9010001 · Cited by 135 · see citing works
Lv, Z., Wang, S., Zhang, F., Chen, L., Hao, X., Pan, Q., Fu, X., Li, L., Sun, X., & Tang, K. (2016) · Plant and Cell Physiology · doi:10.1093/pcp/pcw118 · Cited by 133 · see citing works
Self-citationWang, Y., Zhang, H., Zhao, B., & Yuan, X. (2001) · Biotechnology Letters · doi:10.1023/a:1013786332363 · Cited by 126 · see citing works
Jing, F., Zhang, L., Li, M., Tang, Y., Wang, Y., Wang, Y., Wang, Q., Pan, Q., Wang, G., & Tang, K. (2009) · Biologia · doi:10.2478/s11756-009-0040-8 · Cited by 123 · see citing works
Self-citationYamada, Y., Kokabu, Y., Chaki, K., et al. (2011) · Plant and Cell Physiology · doi:10.1093/pcp/pcr062 · Cited by 99 · see citing works
Wang, H., Ma, C., Li, Z., Ma, L., Wang, H., Ye, H., Xu, G., & Liu, B. (2009) · Industrial Crops and Products · doi:10.1016/j.indcrop.2009.10.008 · Cited by 98 · see citing works
Schweizer, F., Colinas, M., Pollier, J., et al. (2018) · Metabolic Engineering · doi:10.1016/j.ymben.2018.05.016 · Cited by 91 · see citing works
Sears, M. T., Zhang, H., Rushton, P. J., et al. (2013) · Plant Molecular Biology · doi:10.1007/s11103-013-0116-2 · Cited by 89 · see citing works
Elomaa, P., Mehto, M., Kotilainen, M., et al. (1998) · The Plant Journal · doi:10.1046/j.1365-313x.1998.00273.x · Cited by 81 · see citing works
Caretto, S., Quarta, A., Durante, M., Nisi, R., Paolis, A. D., Blando, F., & Mita, G. (2010) · Plant Biology · doi:10.1111/j.1438-8677.2009.00306.x · Cited by 79 · see citing works
Fu, X., Shi, P., He, Q., Shen, Q., Tang, Y., Pan, Q., Ma, Y., Yan, T., Chen, M., Hao, X., et al. (2017) · Frontiers in Plant Science · doi:10.3389/fpls.2017.00723 · Cited by 79 · see citing works
Self-citationWang, H., Han, J., Kanagarajan, S., Lundgren, A., & Brodelius, P. E. (2012) · Plant Molecular Biology · doi:10.1007/s11103-012-9986-y · Cited by 76 · see citing works
Pan, W. S., Zheng, L. P., Tian, H., Li, W. Y., & Wang, J. (2014) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2014.08.013 · Cited by 75 · see citing works
Cold stress improves the production of artemisinin depending on the increase in endogenous jasmonate
Liu, W., Wang, H., Chen, Y., Zhu, S., Chen, M., Lan, X., Chen, G., & Liao, Z. (2017) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.1493 · Cited by 68 · see citing works
Self-citationTranscriptional regulation of artemisinin biosynthesis in Artemisia annua L.
Shen, Q., Yan, T., Fu, X., & Tang, K. (2016) · 中国科学通报:英文版 · doi:10.1007/s11434-015-0983-9 · Cited by 65 · see citing works
Self-citationZhang, F., Xiang, L., Yu, Q., Zhang, H., Zhang, T., Zeng, J., Chen, G., Li, L., Fu, X., Shen, Q., et al. (2017) · Journal of Experimental Botany · doi:10.1093/jxb/erx444 · Cited by 59 · see citing works
Self-citationKurbidaeva, A., Ezhova, T. A., & Novokreshchenova, M. (2014) · Plant Science · doi:10.1016/j.plantsci.2014.08.011 · Cited by 56 · see citing works
AaERF1 Positively Regulates the Resistance to Botrytis cinerea in Artemisia annua
Lu, X., Jiang, W., Zhang, L., Zhang, F., Zhang, F., Shen, Q., Wang, G., & Tang, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057657 · Cited by 54 · see citing works
Self-citationXiang, L., Zhu, S., Zhao, T., Zhang, M., Liu, W., Chen, M., Lan, X., & Liao, Z. (2015) · Plant Growth Regulation · doi:10.1007/s10725-014-0004-z · Cited by 52 · see citing works
Self-citationArtemisia annua: from weed to respectable antimalarial plant
Klayman, D. L. (1993) · Cited by 50 · see citing works
Klayman, D. L. (1993) · ACS symposium series · doi:10.1021/bk-1993-0534.ch017 · Cited by 45 · see citing works
Wang, H., Olofsson, L., Lundgren, A., & Brodelius, P. E. (2011) · American Journal of Plant Sciences · doi:10.4236/ajps.2011.24073 · Cited by 44 · see citing works
Soni, P., & Abdin, M. Z. (2017) · FEBS Open Bio · doi:10.1002/2211-5463.12184 · Cited by 41 · see citing works
Jiang, W., Lu, X., Qiu, B., Zhang, F., Shen, Q., Lv, Z., Fu, X., Yan, T., Gao, E., Zhu, M., et al. (2013) · Plant Molecular Biology Reporter · doi:10.1007/s11105-013-0603-2 · Cited by 34 · see citing works
Self-citationLiu, M., Shi, P., Fu, X., Brodelius, P. E., Shen, Q., Jiang, W., He, Q., & Tang, K. (2016) · Plant Cell Tissue and Organ Culture (PCTOC) · doi:10.1007/s11240-016-1015-4 · Cited by 22 · see citing works
Self-citationBiosynthesis of artemisinin in Artemisia annua induced by low temperature and its mechanism
Yang, R., Lu, Y., Yang, X., et al. (2012) · Zhongcaoyao · Cited by 1 · see citing works
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Wani, K. I., Choudhary, S., Zehra, A., Naeem, M., Weathers, P., & Aftab, T. (2021) · Planta · doi:10.1007/s00425-021-03676-3 · Cited by 74 · see citing works
- Authors
- Xiang, L., Jian, D., Zhang, F., Yang, C., Bai, G., Lan, X., Chen, M., Tang, K., & Liao, Z.
- Affiliations
- Southwest University (CN)
- Tobacco Breeding and Biotechnology Research Center, Yunnan Academy of Tobacco Agricultural Sciences, Key Laboratory of Tobacco Biotechnological Breeding, National Tobacco Genetic Engineering Research Center, Kunming, China
- TAAHC-SWU Medicinal Plant Joint R&D Centre, Xizang Agricultural and Husbandry College, Nyingchi of Tibet, China
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Liao, Zhihua
- Venue
- Journal of Experimental Botany
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-05-14
- Volume
- 70
- Issue
- 18
- Pages
- 4835-4848
- ISSN
- 0022-0957 (ISSN-L)
- 1460-2431
- PMC
- PMC6760284
- OpenAlex
- W2944837707
- Cited by
- 84
- References
- 72
- Citations by year
- 2026: 13 · 2025: 10 · 2024: 14 · 2023: 16 · 2022: 16 · 2021: 13 · 2020: 2
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Experimental Botany (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- NSFC (31770335, 81803660)
- Foundation of YNTC (2016YN22)
- Shanghai Key Discipline Cultivation and Construction Project (ZXDF150005)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant Gene Expression Analysis
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- bHLH transcription factors, artemisinin biosynthesis, eRF1, Artemisia annua, cold stress, transcriptional regulation, AP2/ERF transcription factors, transcriptional activation, low temperature induction
- MeSH terms
- Cold Temperature, Peptide Termination Factors, Phylogeny, Plant Proteins, Plant Leaves, Gene Expression Profiling, Artemisia annua, Flowers, Artemisinins, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Trichomes
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