Regulating the Regulators: The Future Prospects for Transcription-Factor-Based Agricultural Biotechnology Products
Year: 2008
Type: review
Abstract: It is now more than a decade since the first commercially successful genetically engineered agricultural crops were launched (Castle et al., 2006). These first products were based in large part on simple monogenic traits, such as herbicide tolerance or insect resistance, which did not require manipulation of complex molecular pathways in the transgenic plant. Since then, there has been a growing expectation that the biotechnology industry will deliver a second generation of transgenic products for more challenging traits relating to yield and yield stability, which are under complex polygenic control (Gutterson and Zhang, 2004; Salmeron and Herrera-Estrella, 2006). Advances in plant genomics and systems biology, including the availability of the complete genome sequences of both Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa), have offered an unprecedented opportunity to identify regulatory genes and networks that control these important traits. Because transcription factors (TFs) naturally act as master regulators of cellular processes, they are expected to be excellent candidates for modifying complex traits in crop plants, and TF-based technologies are likely to be a prominent part of the next generation of successful biotechnology crops. In this article, we review the prospects for modification of these target traits by TF regulation, including some of the challenges associated with such a strategy. Although transcriptional regulators are being proposed as the wave of the future for agricultural biotechnology, there is strong evidence that TFs have already played a major role in the origin of agriculture through the domestication of various crop plants. This subject is covered in detail in a review by Doebley et al. (2006), with some important examples for three major crops presented here. Probably the most well-known example of a TF with a critical role in a crop domestication trait is that of Teosinte branched1 (Tb1) of maize (Zea mays). Tb1 is a member of the TCP family of TFs, which are generally involved in the regulation of cell proliferation (Cubas et al., 1999). When Tb1 is expressed, it represses the outgrowth of lateral branches; maize plants carrying loss of function alleles produce numerous lateral branches (tillers; Doebley et al., 1997). During the domestication of teosinte to produce maize, an allele was selected that altered the regulation of Tb1, increasing its expression in primary auxiliary meristems. A survey of maize and teosinte alleles at this locus revealed alterations in the regulatory region of the gene and not in the coding sequence (Wang et al., 1999). Thus, selection for cis-regulatory changes that caused a change in expression of a single TF led to the dramatic shift in architecture that underlies the productivity of the most extensively grown crop in modern day North America. Shifts in expression patterns and TF activity have generated important characteristics in other grain crops. In rice, a key trait required for domestication is reduced grain shattering, which prevents the seeds from dropping off the panicles and allows for efficient harvesting of the grain. Two TFs have been identified as playing a major role in reducing grain shattering in domesticated rice plants. One of these was isolated as a quantitative trait locus (QTL) in a cross between a shattering-type ‘Indica’ cultivar and a nonshattering-type ‘Japonica’ (Konishi et al., 2006). This gene, qSH1, encodes a BEL1-type homeodomain protein that is orthologous to Arabidopsis REPLUMLESS (RPL), which is involved in the formation of an abscission zone in the Arabidopsis silique. The QTL is linked to a single nucleotide polymorphism in the regulatory sequences of the gene, not to any change in the coding sequence itself. qSH1 from the shattering cultivar is expressed in the developing abscission layer at the base of the seed, but in the nonshattering cultivar it is not expressed in this location. The expression pattern in other tissues is similar, suggesting that the selection was specifically for loss of expression in the abscission layer. This allele is thought to be an early mutation in the Japonica lineage that was selected during domestication. The other TF affecting this trait is shattering4 (sh4), allelic to sha1 (Li et al., 2006; Lin et al., 2007). SH4 is a member of the trihelix family of plant-specific TFs and was isolated as a major QTL for shattering in a cross between O. sativa and Oryza rufipogon. During domestication, a mutant allele was selected with a single amino acid substitution. Sh4 seems to be necessary for normal separation of the abscission layer that releases the grain from the panicle. For a detailed review of the history of rice domestication, including the role of TFs, the reader is referred to Kovach et al. (2007). Some of the major yield gains achieved by previous generations of conventional crop breeders have subsequently been attributed to alterations in TF activity. Beginning in the 1960s, world wheat (Triticum aestivum) grain yields increased dramatically as farmers started using new, semidwarf varieties of wheat along with “Green Revolution” cultivation practices that included the application of nitrogen fertilizer. With traditional wheat varieties, the application of fertilizer caused the plant to grow too tall, resulting in lodging. The semidwarf varieties, however, did not grow tall with the application of nitrogen, were resistant to lodging caused by wind and rain, and gave an increased grain yield (Silverstone and Sun, 2000). These wheat varieties are short due to a mutation in at least one of two Reduced height-1 loci (Rht-B1 and Rht-D1), which causes the plant to respond abnormally to the hormone GA. Peng et al. (1999) elegantly demonstrated that Rht-B1 and Rht-D1 were orthologs of the Arabidopsis GIBBERELLIN INSENSITIVE (GAI) gene, a member of the GRAS family of TFs, which function as transcriptional repressors of growth that are themselves regulated through inhibition by GAs (Peng et al., 1997; Pysh et al., 1999). The mutations stabilize the protein, causing a semidominant trait for GA insensitivity. Peng et al. (1999) transferred the mutant Arabidopsis gai allele into Basmati rice (normally tall and prone to lodging) and produced dwarf plants. These results confirm that TFs involved in GA insensitivity were selected during conventional wheat breeding and suggest that similar mechanisms can be used to create dwarf varieties of other cereals. There are several further examples of TFs playing major roles in crop improvement via domestication and breeding, generally by way of increasing intrinsic yield through modification of plant architecture (for review, see Doebley et al., 2006; Kovach et al., 2007; Pourkheirandish and Komatsuda, 2007). The question for future biotechnology crops, therefore, is not whether TFs can play an important role, but rather how we can best exploit our current knowledge about molecular pathways regulated by TFs to produce crops with improved agricultural traits. Traditional breeding is limited by the amount of genetic diversity in the germplasm of a particular crop; transgenic technologies bypass genetic barriers, allowing for the possibility of modifying regulatory pathways in one plant using TFs from another plant. Even before the onset of the genomics era, by the early 1990s there was ample evidence that TFs act as master regulators that coordinate the expression of entire response networks of target genes, including numerous examples where a change in activity of a single TF was observed to have a profound effect on an important aspect of plant biology. Well-known examples include the MADS proteins that were shown to control flower development in both Arabidopsis and snapdragon (Antirrhinum majus; Coen and Meyerowitz, 1991), the KNOX class homeodomain proteins that control shoot apical meristem development (Vollbrecht et al., 1991; Long et al., 1996), and the Delila and R genes (HLH family TFs) that control pigmentation in snapdragon and maize, respectively (Goodrich et al., 1992). The availability of the complete Arabidopsis genome sequence and other genomics tools has enabled new reverse genetics strategies for identifying candidate genes for future agricultural biotechnology products. Although there are other gene classes that could be pursued as sources for potentially useful loci for engineering (e.g. signal transduction molecules such as kinases or receptors), TFs in general make particularly attractive targets. These regulators can be broadly defined as proteins that bind DNA and activate or repress the expression of target genes, either directly themselves, or as part of a larger protein complex. There are estimated to be upwards of 1,500 TFs encoded by the Arabidopsis, genome comprising more than 5% of the genes of this plant (Riechmann et al., 2000; Riechmann and Ratcliffe, 2000; Riechmann, 2002; Qu and Zhu, 2006). These TFs can be grouped into different gene families based on DNA-binding domains and other conserved features. Studies of individual TFs have revealed that genes from the same family often regulate similar physiological functions even among very different plant species, and that overall regulation of most biological processes in the plant cell can be linked to one or more TF families (Riechmann and Ratcliffe, 2000; Zhang, 2003; Qu and Zhu, 2006). For these reasons, several research groups in both the and have used genomics strategies to identify TFs with a of biotechnology particularly of the different of crops are of these which not the very that are associated with biotechnology For this are on increasing intrinsic yield and yield in the of in crops and These two general trait on and are major for TF-based genetic The of and future for research in these are can be defined as yield of a cultivar grown in to which it is with and and with and other and The yield in the major crop plants, due to both genetic improvement and changes in cultivation however, suggest that the of yield improvement is off for major crops the for crops such as maize, rice, and could be the of crop traits tolerance to and the overall yield of a but the of the intrinsic yield There are a of that be to intrinsic including increasing modifying plant and the of et al. the of an to identify key of regulation for the of The prospects for plant are by and Long et al. Some of the identified are excellent for TF-based genetic plant architecture to the of is one such in the previous the selection of dwarf wheat varieties and of maize with reduced were in the both of which on modification of processes through mutation or altered regulation of It is therefore, that other TFs involved in plant development could be to produce a that is more efficient at A improved be one in which the allowing for increased in the et al., A of genes involved in the development of plant including several key TFs, is in a review by and using TFs to the response could in a change in plant architecture in some In plants have to for they grow it is for a plant to be in the part of the where availability is In response to the of plant have mechanisms to dramatically architecture to by During a are from and into increased growth and There is a to this of growth in that it can in and is often associated with and a in and plants often at very early of before availability a which can be a particular in crops. This response is to or agricultural but it yield expressed in modern Two TF genes, as and are specifically regulated by changes and play an role in regulation of growth et al., et al., 1999). In TF from the has been to be required for the normal response in Arabidopsis et al., are through a complex of regulatory of which to be and there are examples of of these networks been as to crop yield under it is that transcriptional regulation has a critical role these pathways and they a useful target for future engineering strategies for intrinsic yield include the possibility of modifying regulation to plant growth et al., There is some evidence that expression patterns of the TF genes from Arabidopsis can cell and cell potentially increasing and yield et al., In it has been that an family plant and yield in Arabidopsis, with associated in cell and similar have been observed is in a of such as O. Ratcliffe, and There is evidence that some family TFs and the TFs regulate development et al., et al., et al., 2002; et al., which these families as for another for increasing by for a of A of TFs are involved in including from the and families et al., 2000; et al., and these could be useful for engineering through of these TFs are involved in the response to and other and will be further in a In to intrinsic yield yield to of yield under growth The of are resistance, and of these traits excellent for improvement through transgenic TF and are including and crop a that is as more and more and The for improved tolerance in crop plants is but engineering these traits is particularly challenging complex pathways are involved in the in plants. tolerance in plants has been an of with the of genomics in on the regulatory networks required for This subject has been in numerous et al., 2004; and et al., 2006; 2006; and 2006; et al., 2006; and 2006; and 2006; et al., however, some examples of using TFs to tolerance further different TFs have been in from large TF families including and et al., 2006; et al., Probably the most of TFs involved in and tolerance are the genes as by et al. and et al. (2006), expression of these genes in Arabidopsis, as as in systems such as rice, and et al., 2007; et al., has produced tolerance to one or more of a effect of of the genes is plant growth et al. however, tolerance strong growth by in Arabidopsis under the control of the from the et al. similar results in et al. tolerance in rice plants that either or TF from with the rice increased tolerance and tolerance to The genes, therefore, have a for engineered tolerance in a of plants, the of Arabidopsis as a and as a of useful TF it to be whether the will be in a agricultural The genes produce tolerance by a of pathways that produce physiological that the plant to with and 2002; et al., another TF from has been to produce tolerance in transgenic plants by increasing by the of the plant et al., The same gene and a tolerance in transgenic Arabidopsis plants, as as tolerance in the et al., 2007). the gene from Arabidopsis an family increased and tolerance in transgenic Arabidopsis plants et al., 2004; et al., 2004; et al., 2007). TFs to of such as increased is one for tolerance in crop plants. The Arabidopsis gene is another example of an TF that was to tolerance in transgenic Arabidopsis and rice plants et al., 2007). was isolated by in the but and a with increased of and revealed of in the and in the The and and with the gene a more and more and that were with a and a be as a candidate gene for and intrinsic yield as as The gene another example of a rice TF that can be used to tolerance in transgenic is a family TF that was isolated as a gene and in rice et al., 2006). The increased tolerance in the transgenic grown in and in a and acid be at least for the tolerance in the transgenic plants. In a et al. tolerance in transgenic maize plants through of a member of the family of The Arabidopsis gene was first identified as a in a genomics in plants with the orthologous maize improved tolerance to as by reduced and of under in the transgenic gave grain yields than control under that the pathways regulated by were different from the that tolerance can be achieved through different molecular major to agricultural productivity is plant yield by plant tissues and by to strategies for engineering to plant (for review, see and have on single genes with of the more and signal transduction genes Although some of to be the most important of to not to produce with these a of TFs have been to play a role in conserved response pathways in plants, and are useful for engineering of the of the family in particular have been in the plant response (for review, see and The first that of the be involved in regulation of plant pathways was the of and as with the protein in et al., 1997). Since that genes have been shown to in Arabidopsis or other species, et al., 2002; and and of Arabidopsis et al., 2003; and and of et al., et al., and of et al., et al., 2002; and 2004; et al., and of et al., 2004; et al., of et al., of et al., and of wheat et al., 2007). in several the TF to which be for a Although TFs are for role in some have been as being to For et al. have shown that and can respond to various including and In several TFs that tolerance to various of The first example of this was the gene which was isolated as a gene, and to tolerance and to in et al., and to several other in et al., A of other have now been shown to some of and tolerance which tolerance et al., which tolerance et al., which tolerance et al., which tolerance et al., and which and tolerance et al., 2007). these results that TFs the for engineering both and tolerance in the same plant. TF families in include the and et al., 2000; et al., 2002; and and 2007). These families a large genetic for engineering in crop plants they be used to plant response pathways in a One the response is that it often results in such as growth to has been observed with the genes used in A way this is through the of including and This for engineering plants with is by and and a similar to that which can be for other traits such as as with the used with et al., et al., 2007). is a critical for plants and has to be to crops. The of nitrogen fertilizer to crops the but it a of and can have on the et al., fertilizer that is not by plants is generally as or to nitrogen by to and the nitrogen of crop plants has the to fertilizer application both and A review by et al. to genetically nitrogen in plants. have on in the nitrogen and with of but two TFs were in such and an Arabidopsis MADS family TF that by in Arabidopsis plants in which was an altered to and did not the lateral proliferation by A by the same et al., the expression pattern by and by nitrogen in grown plants, the of lateral growth in was observed in Although the this gene a role in the response to nitrogen and could be useful for response example of the successful engineering of nitrogen using a TF was by et al. the the maize gene, which was to be involved in acid to create transgenic Arabidopsis plants that in amino acid and nitrogen as as improved growth under nitrogen Although nitrogen is one of the most in fertilizer and is the target for in plants, it is that TFs will be used to tolerance to other as an et al. the engineering of tolerance to in rice, using the rice family TF gene of the transgenic improved and shoot and It is that plant TFs are a useful of candidate for new agricultural biotechnology products. however, is the first in the and of developing a new genetically engineered In a review of the application of genomics to biotechnology traits, and a development for an agricultural biotechnology which can to or more from gene to a the of the development there are numerous challenges that be to produce a commercially The first important to a has been identified in a such as Arabidopsis, is whether the target pathways of that TF are in the engineered the examples that have now been for Arabidopsis TFs in systems and the evidence of conserved pathways from among different et al., this is likely to be of a than have been was in the TF technologies often require either to such as growth or to the trait to the at which it is of is by modifying expression of the TF or et al., and rather than the can be to expression of the to the tissues or for the is by protein et al. an example of this by the Arabidopsis protein to a through of regulatory When in transgenic Arabidopsis plants, the produced tolerance the did major for a genetically crop is from regulatory transgenic of a into a crop that is to be in the has to be or by a of the trait and species, include the of the and and the are required from regulatory in other In the current on in by the of were specifically for the first of biotechnology crops, which expressed from sources for herbicide insect resistance, or a for on of biotechnology crops from plant which molecular pathways in the plant. Thus, the of such transgenic crops be expected to be more than for the biotechnology crops. it will be necessary to a of the molecular of for new technologies to that a transgenic plant engineered with an trait new or to the plant from which it was on the examples in this article, it seems to that TFs will be a of the next of agricultural biotechnology intrinsic yield and yield stability, which will the during the next These from during the genomics that in the are expected to deliver gains in yield to achieved through conventional breeding it is likely that further will through of these technologies based on knowledge of molecular of are the prospects for the future and will it to deliver dramatic yield that there is to primary productivity in crop plants. Long et al. in that could a in yield In a more article, et al. an to identify changes in the of among of that are to by in with other crop such as yield and increased could potentially the yield of major crops in the next such however, we will to the of plant gene regulation at a rather than a A decade the plant was in reverse genetics to identify and the function of individual genes in the genome A survey of current that research groups are now at of the genes in the genome into transcription networks which TFs the or protein networks major biological processes, based on and et al., 2007; et al., 2007; et al., 2007; et al., a is in a plant it has to molecular and into both and as such it is a more challenging than for a single cell such as the that have been in single cell systems et al., 2004; et al., 2004; et al., as a for developing such for complex in and are to these and are a for et al., et al., For there are now several and in protein have the to identify the protein of TFs on a large both through in and in et al., 2007; et al., 2007). with these new the to produce systems for plants is being by both the and and major for systems such as for and and the for at potentially important for the best crop and is of regulatory by the various systems a and et al., have of the which is of regulatory This has been used to of a useful to the of alterations in networks on crop the from these systems in it will be to in the networks and identify of genes that can be to produce or on intrinsic yield or yield In will very likely to that can be used to new traits, such as plant in a Long et al. for a of the of change on crop engineering to is another target biotechnology crop (for review, see which we to be by Thus, even biotechnology crops are under a new systems will the that deliver generations of engineered biotechnology crops that will likely be in the second of the that the is expected to by there is a to and even the of improvement in crop to be to and and for such a large intrinsic yield and plant tolerance through genetic engineering will be a critical part of this on the of conventional Because of as master for major regulatory networks and role in the domestication of crop species, TFs are to be among the best and candidate loci for engineering these traits. in systems are expected to the biotechnology including regulation, and traits, of which are likely to have TF useful for The manipulation of plant regulatory networks a new for genetically crops, and we are that and of this will be The our for and and are for on the we to we could not of
Source: PLANT PHYSIOLOGY
Institution: Mendel Biotechnology (United States)
Language: English
Subfield: Plant Science
Domain: Life Sciences
SDG: Zero hunger
Open Access status: bronze
OpenAlex ID: W2109062944