植物bHLH转录因子调控铁稳态的研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2022-1474

摘要/Abstract

摘要：

铁是植物生长发育所必需的微量营养元素，生长在中性或碱性土壤中的植物普遍存在缺铁现象。而植物的正常生长发育需要保持体内铁的平衡，这种铁稳态在转录和转录后水平上都受到严格的调控。植物中铁稳态的调控网络由许多转录因子参与，其中碱性螺旋-环-螺旋（basic helix-loop helix, bHLH）家族的成员不可或缺。本文拟对植物中调控铁平衡的关键bHLH转录因子进行梳理汇总，对这些转录因子在植物生长发育中调节铁稳态的机制进行综述，以期为揭示植物铁稳态调节的研究提供理论基础。

关键词: 铁缺乏, 碱性螺旋-环螺旋家族（bHLH）, 拟南芥, 水稻

Abstract:

Iron is an essential micronutrient for plant growth and development. Iron deficiency is widely existing in plants growing in neutral or alkaline soils. However, the normal growth and development of plants need to maintain the balance of iron，which is tightly regulated at both transcriptional and post-transcriptional levels. Many transcription factors are involved in the regulatory network of iron homeostasis in plants, among which members of the basic helix-loop helix（bHLH）family are essential for iron homeostasis. In this review, key bHLH transcription factors that regulate iron homeostasis are summarized, and the mechanisms by which these transcription factors regulate iron homeostasis in plant growth and development are reviewed, aiming to provide a theoretical basis to uncover the regulation of iron homeostasis in plants.

Key words: iron deficiency, basic helix-loop helix family（bHLH）, Arabidopsis thaliana, rice

李宇, 李素贞, 陈茹梅, 卢海强. 植物bHLH转录因子调控铁稳态的研究进展[J]. 生物技术通报, 2023, 39(7): 26-36.

LI Yu, LI Su-zhen, CHEN Ru-mei, LU Hai-qiang. Advances in the Regulation of Iron Homeostasis by bHLH Transcription Factors in Plant[J]. Biotechnology Bulletin, 2023, 39(7): 26-36.

图/表 4

图1 铁调控网络主要蛋白bHLH结构域图中选取了文中出现过的bHLH蛋白以及典型bHLH蛋白特性的人类蛋白MAS，阴影框里分别表示DNA结合碱性区域、两个α螺旋和一个环区

Fig. 1 Alignment of the bHLH domain of iron-regulated network main proteins The bHLH protein mentioned in the text and the typical human protein MAS with bHLH protein characteristics were selected in the figure. The shaded boxes represent the DNA binding alkaline region and two α spiral and a circular region

图2 拟南芥中铁稳态调控

Fig. 2 Fe homeostasis regulation in Arabidopsis

图3 拟南芥和水稻中调控铁稳态的bHLH转录因子进化树

Fig. 3 Phylogenetic tree of bHLH TFs regulating Fe homeostasis in Arabidopsis and rice（Oryza sativa）

图4 水稻中铁稳态机制

Fig. 4 Fe homeostasis mechanism in rice

参考文献 60

[1]	Wintz H, Fox T, Wu YY, et al. Expression profiles of Arabidopsis thaliana in mineral deficiencies reveal novel transporters involved in metal homeostasis[J]. J Biol Chem, 2003, 278(48): 47644-47653. doi: 10.1074/jbc.M309338200 URL
[2]	Briat JF, Dubos C, Gaymard F. Iron nutrition, biomass production, and plant product quality[J]. Trends Plant Sci, 2015, 20(1): 33-40. doi: 10.1016/j.tplants.2014.07.005 URL
[3]	Römheld V, Marschner H. Evidence for a specific uptake system for iron phytosiderophores in roots of grasses[J]. Plant Physiol, 1986, 80(1): 175-180. doi: 10.1104/pp.80.1.175 pmid: 16664577
[4]	Kobayashi T, Nishizawa NK. Iron uptake, translocation, and regulation in higher plants[J]. Annu Rev Plant Biol, 2012, 63: 131-152. doi: 10.1146/annurev-arplant-042811-105522 pmid: 22404471
[5]	Gao F, Dubos C. Transcriptional integration of plant responses to iron availability[J]. J Exp Bot, 2021, 72(6): 2056-2070. doi: 10.1093/jxb/eraa556 pmid: 33246334
[6]	Fourcroy P, Tissot N, Gaymard F, et al. Facilitated Fe nutrition by phenolic compounds excreted by the Arabidopsis ABCG37/PDR9 transporter requires the IRT1/FRO2 high-affinity root Fe(2+)transport system[J]. Mol Plant, 2016, 9(3): 485-488. doi: S1674-2052(15)00387-1 pmid: 26415695
[7]	Robinson NJ, Procter CM, Connolly EL, et al. A ferric-chelate reductase for iron uptake from soils[J]. Nature, 1999, 397(6721): 694-697. doi: 10.1038/17800 URL
[8]	Brumbarova T, Bauer P, Ivanov R. Molecular mechanisms governing Arabidopsis iron uptake[J]. Trends Plant Sci, 2015, 20(2): 124-133. doi: 10.1016/j.tplants.2014.11.004 pmid: 25499025
[9]	Curie C, Panaviene Z, Loulergue C, et al. Maize yellow stripe1 encodes a membrane protein directly involved in Fe(III)uptake[J]. Nature, 2001, 409(6818): 346-349. doi: 10.1038/35053080 URL
[10]	Zheng LQ, Ying YH, Wang L, et al. Identification of a novel iron regulated basic helix-loop-helix protein involved in Fe homeostasis in Oryza sativa[J]. BMC Plant Biol, 2010, 10: 166. doi: 10.1186/1471-2229-10-166
[11]	Heim MA, Jakoby M, Werber M, et al. The basic helix-loop-helix transcription factor family in plants: a genome-wide study of protein structure and functional diversity[J]. Mol Biol Evol, 2003, 20(5): 735-747. doi: 10.1093/molbev/msg088 pmid: 12679534
[12]	Li XX, Duan XP, Jiang HX, et al. Genome-wide analysis of basic/helix-loop-helix transcription factor family in rice and Arabidopsis[J]. Plant Physiol, 2006, 141(4): 1167-1184. doi: 10.1104/pp.106.080580 URL
[13]	Tarczewska A, Greb-Markiewicz B. The significance of the intrinsically disordered regions for the functions of the bHLH transcription factors[J]. Int J Mol Sci, 2019, 20(21): 5306. doi: 10.3390/ijms20215306 URL
[14]	Pires N, Dolan L. Origin and diversification of basic-helix-loop-helix proteins in plants[J]. Mol Biol Evol, 2010, 27(4): 862-874. doi: 10.1093/molbev/msp288 pmid: 19942615
[15]	Hao YQ, Zong XM, Ren P, et al. Basic helix-loop-helix(bHLH)transcription factors regulate a wide range of functions in Arabidopsis[J]. Int J Mol Sci, 2021, 22(13): 7152. doi: 10.3390/ijms22137152 URL
[16]	Filiz E, Vatansever R, Ozyigit II. Dissecting a co-expression network of basic helix-loop-helix(bHLH)genes from phosphate(Pi)-starved soybean(Glycine max)[J]. Plant Gene, 2017, 9: 19-25. doi: 10.1016/j.plgene.2016.12.001 URL
[17]	Gao F, Robe K, Gaymard F, et al. The transcriptional control of iron homeostasis in plants: a tale of bHLH transcription factors?[J]. Front Plant Sci, 2019, 10: 6. doi: 10.3389/fpls.2019.00006 pmid: 30713541
[18]	Gao F, Robe K, Bettembourg M, et al. The transcription factor bHLH121 interacts with bHLH105(ILR3)and its closest homologs to regulate iron homeostasis in Arabidopsis[J]. Plant Cell, 2020, 32(2): 508-524. doi: 10.1105/tpc.19.00541 URL
[19]	Selote D, Samira R, Matthiadis A, et al. Iron-binding E3 ligase mediates iron response in plants by targeting basic helix-loop-helix transcription factors[J]. Plant Physiol, 2015, 167(1): 273-286. doi: 10.1104/pp.114.250837 pmid: 25452667
[20]	Rodríguez-Celma J, Connorton JM, Kruse I, et al. Arabidopsis BRUTUS-LIKE E3 ligases negatively regulate iron uptake by targeting transcription factor FIT for recycling[J]. Proc Natl Acad Sci USA, 2019, 116(35): 17584-17591. doi: 10.1073/pnas.1907971116 pmid: 31413196
[21]	Wang N, Cui Y, Liu Y, et al. Requirement and functional redundancy of Ib subgroup bHLH proteins for iron deficiency responses and uptake in Arabidopsis thaliana[J]. Mol Plant, 2013, 6(2): 503-513. doi: 10.1093/mp/sss089 URL
[22]	Akmakjian GZ, Riaz N, Guerinot ML. Photoprotection during iron deficiency is mediated by the bHLH transcription factors PYE and ILR3[J]. Proc Natl Acad Sci USA, 2021, 118(40): e2024918118.
[23]	Liang G, Zhang HM, Li XL, et al. bHLH transcription factor bHLH115 regulates iron homeostasis in Arabidopsis thaliana[J]. J Exp Bot, 2017, 68(7): 1743-1755. doi: 10.1093/jxb/erx043 pmid: 28369511
[24]	Li XL, Zhang HM, Ai Q, et al. Two bHLH transcription factors, bHLH34 and bHLH104, regulate iron homeostasis in Arabidopsis thaliana[J]. Plant Physiol, 2016, 170(4): 2478-2493. doi: 10.1104/pp.15.01827 URL
[25]	Lei RH, Li Y, Cai YR, et al. bHLH121 functions as a direct link that facilitates the activation of FIT by bHLH IVc transcription factors for maintaining Fe homeostasis in Arabidopsis[J]. Mol Plant, 2020, 13(4): 634-649. doi: 10.1016/j.molp.2020.01.006 URL
[26]	Gao F, Robe K, Dubos C. Further insights into the role of bHLH121 in the regulation of iron homeostasis in Arabidopsis thaliana[J]. Plant Signal Behav, 2020, 15(10): 1795582. doi: 10.1080/15592324.2020.1795582 URL
[27]	Schwarz B, Bauer P. FIT, a regulatory hub for iron deficiency and stress signaling in roots, and FIT-dependent and-independent gene signatures[J]. J Exp Bot, 2020, 71(5): 1694-1705. doi: 10.1093/jxb/eraa012 pmid: 31922570
[28]	Bauer P, Ling HQ, Guerinot ML. Fit, the fer-like iron deficiency induced transcription factor in Arabidopsis[J]. Plant Physiol Biochem, 2007, 45(5): 260-261. doi: 10.1016/j.plaphy.2007.03.006 URL
[29]	Sivitz AB, Hermand V, Curie C, et al. Arabidopsis bHLH100 and bHLH101 control iron homeostasis via a FIT-independent pathway[J]. PLoS One, 2012, 7(9): e44843.
[30]	Yuan YX, Wu HL, Wang N, et al. FIT interacts with AtbHLH38 and AtbHLH39 in regulating iron uptake gene expression for iron homeostasis in Arabidopsis[J]. Cell Res, 2008, 18(3): 385-397.
[31]	Long TA, Tsukagoshi H, Busch W, et al. The bHLH transcription factor POPEYE regulates response to iron deficiency in Arabidopsis roots[J]. Plant Cell, 2010, 22(7): 2219-2236. doi: 10.1105/tpc.110.074096 URL
[32]	Tanabe N, Noshi M, Mori D, et al. The basic helix-loop-helix transcription factor, bHLH11 functions in the iron-uptake system in Arabidopsis thaliana[J]. J Plant Res, 2019, 132(1): 93-105. doi: 10.1007/s10265-018-1068-z
[33]	Gratz R, Manishankar P, Ivanov R, et al. CIPK11-dependent phosphorylation modulates FIT activity to promote Arabidopsis iron acquisition in response to calcium signaling[J]. Dev Cell, 2019, 48(5): 726-740.e10. doi: 10.1016/j.devcel.2019.01.006 URL
[34]	Gratz R, Brumbarova T, Ivanov R, et al. Phospho-mutant activity assays provide evidence for alternative phospho-regulation pathways of the transcription factor fer-like iron deficiency-induced transcription factor[J]. New Phytol, 2020, 225(1): 250-267. doi: 10.1111/nph.16168 pmid: 31487399
[35]	Cui Y, Chen CL, Cui M, et al. Four IVa bHLH transcription factors are novel interactors of FIT and mediate JA inhibition of iron uptake in Arabidopsis[J]. Mol Plant, 2018, 11(9): 1166-1183. doi: 10.1016/j.molp.2018.06.005 URL
[36]	Matsuoka K, Furukawa J, Bidadi H, et al. Gibberellin-induced expression of Fe uptake-related genes in Arabidopsis[J]. Plant Cell Physiol, 2014, 55(1): 87-98. doi: 10.1093/pcp/pct160 pmid: 24192296
[37]	Wild M, Davière JM, Regnault T, et al. Tissue-specific regulation of gibberellin signaling fine-tunes Arabidopsis iron-deficiency responses[J]. Dev Cell, 2016, 37(2): 190-200. doi: 10.1016/j.devcel.2016.03.022 URL
[38]	Chao Q, Rothenberg M, Solano R, et al. Activation of the ethylene gas response pathway in Arabidopsis by the nuclear protein ETHYLENE-INSENSITIVE3 and related proteins[J]. Cell, 1997, 89(7): 1133-1144. doi: 10.1016/s0092-8674(00)80300-1 pmid: 9215635
[39]	Lingam S, Mohrbacher J, Brumbarova T, et al. Interaction between the bHLH transcription factor FIT and ETHYLENE INSENSITIVE3/ETHYLENE INSENSITIVE3-LIKE1 reveals molecular linkage between the regulation of iron acquisition and ethylene signaling in Arabidopsis[J]. Plant Cell, 2011, 23(5): 1815-1829. doi: 10.1105/tpc.111.084715 URL
[40]	Yang Y, Ou B, Zhang JZ, et al. The Arabidopsis mediator subunit MED16 regulates iron homeostasis by associating with EIN3/EIL1 through subunit MED25[J]. Plant J, 2014, 77(6): 838-851. doi: 10.1111/tpj.2014.77.issue-6 URL
[41]	Zhang Y, Wu HL, Wang N, et al. Mediator subunit 16 functions in the regulation of iron uptake gene expression in Arabidopsis[J]. New Phytol, 2014, 203(3): 770-783. doi: 10.1111/nph.12860 pmid: 24889527
[42]	Ishimaru Y, Suzuki M, Tsukamoto T, et al. Rice plants take up iron as an Fe³⁺-phytosiderophore and as Fe²⁺[J]. Plant J, 2006, 45(3): 335-346. doi: 10.1111/j.1365-313X.2005.02624.x pmid: 16412081
[43]	Zhang HM, Li Y, Pu MN, et al. Oryza sativa positive regulator of iron deficiency response 2(ospri2)and ospri3 are involved in the maintenance of fe homeostasis[J]. Plant Cell Environ, 2020, 43(1): 261-274. doi: 10.1111/pce.v43.1 URL
[44]	Kobayashi T, Nagasaka S, Senoura T, et al. Iron-binding haemerythrin RING ubiquitin ligases regulate plant iron responses and accumulation[J]. Nat Commun, 2013, 4: 2792. doi: 10.1038/ncomms3792 pmid: 24253678
[45]	Zhang HM, Li Y, Yao XN, et al. POSITIVE REGULATOR OF IRON HOMEOSTASIS1, OsPRI1, facilitates iron homeostasis[J]. Plant Physiol, 2017, 175(1): 543-554. doi: 10.1104/pp.17.00794 pmid: 28751317
[46]	Wang WJ, Ye J, Ma YR, et al. OsIRO3 plays an essential role in iron deficiency responses and regulates iron homeostasis in rice[J]. Plants(Basel), 2020, 9(9): 1095.
[47]	Wang WJ, Ye J, Xu H, et al. osbhlh061 links topless/topless-related repressor proteins with positive regulator of iron homeostasis 1 to maintain iron homeostasis in rice[J]. New Phytol, 2022, 234(5): 1753-1769. doi: 10.1111/nph.18096 pmid: 35288933
[48]	Ogo Y, Itai RN, Kobayashi T, et al. OsIRO2 is responsible for iron utilization in rice and improves growth and yield in calcareous soil[J]. Plant Mol Biol, 2011, 75(6): 593-605. doi: 10.1007/s11103-011-9752-6 pmid: 21331630
[49]	Ogo Y, Itai RN, Nakanishi H, et al. The rice bHLH protein OsIRO2 is an essential regulator of the genes involved in Fe uptake under Fe-deficient conditions[J]. Plant J, 2007, 51(3): 366-377. doi: 10.1111/j.1365-313X.2007.03149.x pmid: 17559517
[50]	Li CY, Li Y, Xu P, et al. OsIRO3 negatively regulates Fe homeostasis by repressing the expression of OsIRO2[J]. Plant J, 2022, 111(4): 966-978. doi: 10.1111/tpj.v111.4 URL
[51]	Wang SD, Li L, Ying YH, et al. A transcription factor OsbHLH156 regulates Strategy II iron acquisition through localising IRO2 to the nucleus in rice[J]. New Phytol, 2020, 225(3): 1247-1260. doi: 10.1111/nph.16232 pmid: 31574173
[52]	Trofimov K, Ivanov R, Eutebach M, et al. Mobility and localization of the iron deficiency-induced transcription factor bHLH039 change in the presence of FIT[J]. Plant Direct, 2019, 3(12): e00190.
[53]	Brumbarova T, Bauer P. Iron-mediated control of the basic helix-loop-helix protein FER, a regulator of iron uptake in tomato[J]. Plant Physiol, 2005, 137(3): 1018-1026. doi: 10.1104/pp.104.054270 pmid: 15695640
[54]	Bereczky Z, Wang HY, Schubert V, et al. Differential regulation of nramp and irt metal transporter genes in wild type and iron uptake mutants of tomato[J]. J Biol Chem, 2003, 278(27): 24697-24704. doi: 10.1074/jbc.M301365200 pmid: 12709425
[55]	Du J, Huang ZA, Wang B, et al. SlbHLH068 interacts with FER to regulate the iron-deficiency response in tomato[J]. Ann Bot, 2015, 116(1): 23-34. doi: 10.1093/aob/mcv058 URL
[56]	Zhao Q, Ren YR, Wang QJ, et al. Overexpression of MdbHLH104 gene enhances the tolerance to iron deficiency in apple[J]. Plant Biotechnol J, 2016, 14(7): 1633-1645. doi: 10.1111/pbi.2016.14.issue-7 URL
[57]	Xu HM, Wang Y, Chen F, et al. Isolation and characterization of the iron-regulated MxbHLH01 gene in Malus xiaojinensis[J]. Plant Mol Biol Rep, 2011, 29(4): 936-942. doi: 10.1007/s11105-011-0305-6 URL
[58]	Yin L, Wang Y, Yan M, et al. Molecular cloning, polyclonal antibody preparation, and characterization of a functional iron-related transcription factor IRO2 from Malus xiaojinensis[J]. Plant Physiol Biochem, 2013, 67: 63-70. doi: 10.1016/j.plaphy.2013.02.021 URL
[59]	Tian Y, Pu XD, Yu HY, et al. Genome-wide characterization and analysis of bHLH transcription factors related to crocin biosynthesis in Gardenia jasminoides Ellis(Rubiaceae)[J]. Biomed Res Int, 2020, 2020: 2903861.
[60]	Ling HQ, Bauer P, Bereczky Z, et al. The tomato fer gene encoding a bHLH protein controls iron-uptake responses in roots[J]. Proc Natl Acad Sci USA, 2002, 99(21): 13938-13943. doi: 10.1073/pnas.212448699 URL