NEWS & VIEWS
doi:10.1038/nature14085
provides a huge number of combinatorial pos sibilities, which Taylor-Teeples and colleagues show is crucial for integrating environmental signals such as salt or iron stress — alterations in the expression of certain transcription factors allowed different sub-networks to be used to adapt the cellular response to these conditions. The network also reveals that many of the The identification of the gene regulatory network that controls the formation transcription factors are not part of simple of xylem — the major component of wood — opens up new avenues for linear pathways, but form a series of feedmanipulating plant biomass. forward loops (FFLs). Such regulatory sys tems are well recognized in systems biology, and typically involve a transcription factor that A N T H O N Y B I S H O P P & M A L C O L M J . B E N N E T T xylem-associated transcription factors and controls the expression of other transcription their gene targets. factors, which then collectively co-regulate ellulose, hemicelluloses and lignin are Taylor-Teeples et al. instead adopted a their target genes. For example, the authors key natural polymers that make up the network approach — screening more than find that the transcription factor E2Fc binds bulk of plant biomass1. These biopoly 460 transcription factors expressed in the root to more than 20 promoters, including those for mers are also renewable resources for the xylem of A. thaliana for their ability to bind the the genes encoding the transcription factors production of dietary fibre, paper and bio promoters of around 50 previously character VND6, VND7 and MYB46, as well as genes fuels2. In a paper published on Nature’s website ized genes that encode cell-wall components or associated with cellulose, hemicellulose and today, Taylor-Teeples et al.3 report the identi other transcription factors involved in xylem lignin production. Although FFLs are com fication of the gene regulatory network that formation. This large-scale analysis provided a mon in biological systems5, they are remarka controls the synthesis of these biopolymers in remarkable overview of the regulatory process, bly numerous in the xylem network, occurring root xylem cells of the model plant Arabidopsis revealing a highly interconnected network close to 100 times. They are also frequently thaliana. composed of some 240 genes and more than embedded within one another, creating FFL Xylem is a plant tissue that provides 600 new protein–DNA interactions. cascades. For example, the network shows that mechanical support and the main mechanism The xylem regulatory network shows that VND7 and MYB46 also bind to the promoters for transporting water and nutrients from each cell-wall gene is bound, on average, by of many E2Fc target genes. root to shoot tissues. To perform these impor 5 different transcription factors, each belong So why are there so many FFLs? Not only tant functions, xylem cells deposit a specially ing to one of 35 distinct families of regula are there many possible components, but reinforced structure termed the secondary cell tory proteins. This regulatory arrangement even for simple systems with only three com wall1 (Fig. 1). Xylem secondary cell walls ponents, there are many possible ways to are composed mainly of cellulose, hemi wire them6. Common to all FFLs is a direct celluloses and lignin. The cellulose forms path (in which a source transcription fac a network of load-bearing fibres coated in tor regulates a target gene) and an indi hemicelluloses and embedded in lignin, rect path (in which the same source factor Xylem cell providing mechanical strength and rigid regulates an intermediate transcription Granular matrix ity (akin to steel rods set in reinforced con factor that regulates the same target). crete). However, the presence of lignin is a For ‘coherent’ FFLs, the direct and indi Primary major impediment to efficient extraction of rect paths have the same overall effect on cell wall the sugars in cellulose and hemicelluloses the target gene (both activate or repress its for their conversion to biofuels2. Hence, expression), whereas for incoherent FFLs, Secondary understanding how the relative propor one path activates and the other represses. cell wall tions of these biopolymers are controlled in Mathematical modelling of these loops has plant tissue would open up opportunities to revealed that different arrangements can redesign plants for biofuel use. produce a range of responses from target Xylem cells control the relative abundance genes. For example, coherent FFLs can of biopolymers in part by regulating expres protect against unwanted responses to fluc sion of the genes that encode the enzymes tuations in inputs, whereas incoherent FFLs for polymer synthesis4. Expression is con can speed up transcriptional responses6. In trolled by transcription-factor proteins the case of the xylem network, a coher that bind DNA sequences, termed pro ent FFL could result in tight regulation moters, close to the genes. A handful of Figure 1 | Building a secondary cell wall. The cell wall of cell-wall gene expression, thereby pro transcription factors have been identified of plant xylem cells (a tracheary-element cell is shown) moting secondary cell-wall synthesis in a contains several layers, including an outer granular that control the expression of individual switch-like manner to prevent the depo matrix, a primary cell wall composed mainly of the genes regulating the production of cel biopolymer cellulose and an inner secondary cell wall sition of secondary cell-wall material in lulose, hemicelluloses and lignin. But this composed of microfibrils of cellulose and lignin. Taylornon-xylem cells. small-scale, gene-by-gene approach has Teeples et al.3 have characterized the gene regulatory It is not yet possible to determine provided a highly fragmented picture of the network that determines the production of xylem exactly what types of FFL are present in potential regulatory interactions between biopolymers. the xylem regulatory network described P L AN T B IO LO GY
Seeing the wood and the trees
C
| NAT U R E | 1
© 2014 Macmillan Publishers Limited. All rights reserved
RESEARCH NEWS & VIEWS by Taylor-Teeples et al., because although the technology used by the authors identifies interactive nodes, it cannot predict whether they relate to transcriptional activation or repression. However, these nodes provide a framework for future research to characterize key interactions in a targeted, gene-by-gene manner, and to determine the precise regula tory structure. This will allow the identification of ways to manipulate this network to engineer different cellular properties and develop new plant varieties for biofuel use. The description
of the network also helps to explain why plant transcription factors have so far largely eluded identification by genetic screens, owing to functional redundancy among regulators of secondary-cell-wall biosynthesis. This knowledge can now be used to perform moreprecisely targeted screens of gene function, by creating combinations of mutations that over come this genetic redundancy. ■ Anthony Bishopp and Malcolm J. Bennett are in the Centre for Plant Integrative Biology,
2 | NAT U R E |
© 2014 Macmillan Publishers Limited. All rights reserved
University of Nottingham, Sutton Bonington LE12 5RD, UK. e-mails: [email protected]; [email protected] 1. Turner, S., Gallois, P. & Brown, D. Annu. Rev. Plant Biol. 58, 407–433 (2007). 2. Somerville, C., Youngs, H., Taylor, C., Davis, S. C. & Long, S. P. Science 329, 790–792 (2010). 3. Taylor-Teeples, M. et al. Nature http://dx.doi. org/10.1038/nature14099 (2014). 4. Kondo, Y., Tamaki, T. & Fukuda, H. Front. Plant Sci. 5, 315 (2014). 5. Milo, R. et al. Science 298, 824–827 (2002). 6. Alon, U. Nature Rev. Genet. 8, 450–461 (2007).
doi:10.1038/nature14085
provides a huge number of combinatorial pos sibilities, which Taylor-Teeples and colleagues show is crucial for integrating environmental signals such as salt or iron stress — alterations in the expression of certain transcription factors allowed different sub-networks to be used to adapt the cellular response to these conditions. The network also reveals that many of the The identification of the gene regulatory network that controls the formation transcription factors are not part of simple of xylem — the major component of wood — opens up new avenues for linear pathways, but form a series of feedmanipulating plant biomass. forward loops (FFLs). Such regulatory sys tems are well recognized in systems biology, and typically involve a transcription factor that A N T H O N Y B I S H O P P & M A L C O L M J . B E N N E T T xylem-associated transcription factors and controls the expression of other transcription their gene targets. factors, which then collectively co-regulate ellulose, hemicelluloses and lignin are Taylor-Teeples et al. instead adopted a their target genes. For example, the authors key natural polymers that make up the network approach — screening more than find that the transcription factor E2Fc binds bulk of plant biomass1. These biopoly 460 transcription factors expressed in the root to more than 20 promoters, including those for mers are also renewable resources for the xylem of A. thaliana for their ability to bind the the genes encoding the transcription factors production of dietary fibre, paper and bio promoters of around 50 previously character VND6, VND7 and MYB46, as well as genes fuels2. In a paper published on Nature’s website ized genes that encode cell-wall components or associated with cellulose, hemicellulose and today, Taylor-Teeples et al.3 report the identi other transcription factors involved in xylem lignin production. Although FFLs are com fication of the gene regulatory network that formation. This large-scale analysis provided a mon in biological systems5, they are remarka controls the synthesis of these biopolymers in remarkable overview of the regulatory process, bly numerous in the xylem network, occurring root xylem cells of the model plant Arabidopsis revealing a highly interconnected network close to 100 times. They are also frequently thaliana. composed of some 240 genes and more than embedded within one another, creating FFL Xylem is a plant tissue that provides 600 new protein–DNA interactions. cascades. For example, the network shows that mechanical support and the main mechanism The xylem regulatory network shows that VND7 and MYB46 also bind to the promoters for transporting water and nutrients from each cell-wall gene is bound, on average, by of many E2Fc target genes. root to shoot tissues. To perform these impor 5 different transcription factors, each belong So why are there so many FFLs? Not only tant functions, xylem cells deposit a specially ing to one of 35 distinct families of regula are there many possible components, but reinforced structure termed the secondary cell tory proteins. This regulatory arrangement even for simple systems with only three com wall1 (Fig. 1). Xylem secondary cell walls ponents, there are many possible ways to are composed mainly of cellulose, hemi wire them6. Common to all FFLs is a direct celluloses and lignin. The cellulose forms path (in which a source transcription fac a network of load-bearing fibres coated in tor regulates a target gene) and an indi hemicelluloses and embedded in lignin, rect path (in which the same source factor Xylem cell providing mechanical strength and rigid regulates an intermediate transcription Granular matrix ity (akin to steel rods set in reinforced con factor that regulates the same target). crete). However, the presence of lignin is a For ‘coherent’ FFLs, the direct and indi Primary major impediment to efficient extraction of rect paths have the same overall effect on cell wall the sugars in cellulose and hemicelluloses the target gene (both activate or repress its for their conversion to biofuels2. Hence, expression), whereas for incoherent FFLs, Secondary understanding how the relative propor one path activates and the other represses. cell wall tions of these biopolymers are controlled in Mathematical modelling of these loops has plant tissue would open up opportunities to revealed that different arrangements can redesign plants for biofuel use. produce a range of responses from target Xylem cells control the relative abundance genes. For example, coherent FFLs can of biopolymers in part by regulating expres protect against unwanted responses to fluc sion of the genes that encode the enzymes tuations in inputs, whereas incoherent FFLs for polymer synthesis4. Expression is con can speed up transcriptional responses6. In trolled by transcription-factor proteins the case of the xylem network, a coher that bind DNA sequences, termed pro ent FFL could result in tight regulation moters, close to the genes. A handful of Figure 1 | Building a secondary cell wall. The cell wall of cell-wall gene expression, thereby pro transcription factors have been identified of plant xylem cells (a tracheary-element cell is shown) moting secondary cell-wall synthesis in a contains several layers, including an outer granular that control the expression of individual switch-like manner to prevent the depo matrix, a primary cell wall composed mainly of the genes regulating the production of cel biopolymer cellulose and an inner secondary cell wall sition of secondary cell-wall material in lulose, hemicelluloses and lignin. But this composed of microfibrils of cellulose and lignin. Taylornon-xylem cells. small-scale, gene-by-gene approach has Teeples et al.3 have characterized the gene regulatory It is not yet possible to determine provided a highly fragmented picture of the network that determines the production of xylem exactly what types of FFL are present in potential regulatory interactions between biopolymers. the xylem regulatory network described P L AN T B IO LO GY
Seeing the wood and the trees
C
| NAT U R E | 1
© 2014 Macmillan Publishers Limited. All rights reserved
RESEARCH NEWS & VIEWS by Taylor-Teeples et al., because although the technology used by the authors identifies interactive nodes, it cannot predict whether they relate to transcriptional activation or repression. However, these nodes provide a framework for future research to characterize key interactions in a targeted, gene-by-gene manner, and to determine the precise regula tory structure. This will allow the identification of ways to manipulate this network to engineer different cellular properties and develop new plant varieties for biofuel use. The description
of the network also helps to explain why plant transcription factors have so far largely eluded identification by genetic screens, owing to functional redundancy among regulators of secondary-cell-wall biosynthesis. This knowledge can now be used to perform moreprecisely targeted screens of gene function, by creating combinations of mutations that over come this genetic redundancy. ■ Anthony Bishopp and Malcolm J. Bennett are in the Centre for Plant Integrative Biology,
2 | NAT U R E |
© 2014 Macmillan Publishers Limited. All rights reserved
University of Nottingham, Sutton Bonington LE12 5RD, UK. e-mails: [email protected]; [email protected] 1. Turner, S., Gallois, P. & Brown, D. Annu. Rev. Plant Biol. 58, 407–433 (2007). 2. Somerville, C., Youngs, H., Taylor, C., Davis, S. C. & Long, S. P. Science 329, 790–792 (2010). 3. Taylor-Teeples, M. et al. Nature http://dx.doi. org/10.1038/nature14099 (2014). 4. Kondo, Y., Tamaki, T. & Fukuda, H. Front. Plant Sci. 5, 315 (2014). 5. Milo, R. et al. Science 298, 824–827 (2002). 6. Alon, U. Nature Rev. Genet. 8, 450–461 (2007).
