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Results for “Transcription Activator-Like Effectors”

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PubMed2026

TALEs, TALENs, and TALE Base Editors: From Plant Pathology to Biotechnology.

TALEs (transcription activator-like effectors) are an excellent example of how studying pathogen-host interactions can lead to significant biotechnology inventions. TALEs are bacterial effectors that are translocated into plant cells via a bacterial type III secretion system. Once inside the host cell, they are imported into the nucleus to bind specific promoters and induce expression of target genes, thereby supporting the bacterial infection. TALEs are found throughout many, but not all, Xanthomonas pathovars, which can be severe pathogens of different crops. The key feature of TALEs is their modular DNA-binding domain, which allows a simple evolutionary adaptation to novel DNA sequences as well as simple cloning of designer TALEs with desired DNA-binding specificity. Accordingly, TALE nucleases started the genome-editing revolution, and TALE base editors are the latest tools to efficiently edit chloroplast and mitochondrial genomes. We review recent advances in Xanthomonas genomics, synthesize current knowledge about naturally occurring TALEs, and highlight current roles of TALEs in genome editing and synthetic biology.

Xanthomonas↗
PubMed2024

Designer TALEs enable discovery of cell death-inducer genes.

Transcription activator-like effectors (TALEs) in plant-pathogenic Xanthomonas bacteria activate expression of plant genes and support infection or cause a resistance response. PthA4AT is a TALE with a particularly short DNA-binding domain harboring only 7.5 repeats which triggers cell death in Nicotiana benthamiana; however, the genetic basis for this remains unknown. To identify possible target genes of PthA4AT that mediate cell death in N. benthamiana, we exploited the modularity of TALEs to stepwise enhance their specificity and reduce potential target sites. Substitutions of individual repeats suggested that PthA4AT-dependent cell death is sequence specific. Stepwise addition of repeats to the C-terminal or N-terminal end of the repeat region narrowed the sequence requirements in promoters of target genes. Transcriptome profiling and in silico target prediction allowed the isolation of two cell death inducer genes, which encode a patatin-like protein and a bifunctional monodehydroascorbate reductase/carbonic anhydrase protein. These two proteins are not linked to known TALE-dependent resistance genes. Our results show that the aberrant expression of different endogenous plant genes can cause a cell death reaction, which supports the hypothesis that TALE-dependent executor resistance genes can originate from various plant processes. Our strategy further demonstrates the use of TALEs to scan genomes for genes triggering cell death and other relevant phenotypes.

Cell Death↗
PubMed2026

Two domesticated species of rice shaped the population structure of Xanthomonas oryzae pv. oryzae in Africa.

African rice (Oryza glaberrima) was independently domesticated in West Africa around 3000 years ago, and has long been intertwined in the history of the region. Asian rice (Oryza sativa), which was introduced in Africa when European settlers arrived, gradually replaced African rice and has since dominated rice cultivation in the continent. Domesticated rice species are affected by bacterial leaf blight (BLB), which is caused by the pathogen Xanthomonas oryzae pv. oryzae (Xoo). Here we show that the bacterial leaf blight pathogen in Africa (AfXoo) belongs to a distinct phylogroup from the one circulating in Asia (AsXoo), and has a different evolutionary history. Analysis of 87 AfXoo genomes identified five main populations, including highly clonal ones, and a more diverse and recombinant population. Tip-dating analysis revealed that the AfXoo population went through a period of expansion, then decline and more recent recovery. We hypothesize this followed the rise and fall of African rice, and that the introduction of O. sativa served as a bottleneck leading to the emergence of current AfXoo populations. We show that AfXoo has a highly conserved repertoire of type III effectors (T3E), but that nonetheless there is variation especially between populations. In the case of transcription activator-like effectors (TALEs), variation can arise quickly through rearrangements, and we hypothesize that the TALE repertoire of AfXoo has been selected to allow the bacteria to colonize both species of cultivated rice found in the continent. Our research provides an attempt to decipher the genetic history of bacterial blight in West Africa, and its past and present impact on rice cultivation in the region.

Journal Article↗
PubMed2025

Design of optimized epigenetic regulators for durable gene silencing with application to PCSK9 in nonhuman primates.

Epigenetic editing is a promising strategy for modifying gene expression while avoiding the permanent alterations and potential genotoxicity of genome-editing technologies. Here we designed optimized epigenetic regulators (EpiRegs) by testing combinations of transcription activator-like effector (TALE)-based and catalytically deactivated Cas9 (dCas9)-based epigenetic modification effectors and fusion protein structures. TALE-based EpiReg (EpiReg-T) achieved a final efficiency of 98% in mice, surpassing the initial dCas9-based efficiency of 64%. We demonstrated the approach in macaques by introducing DNA methylation and histone modifications to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) expression, thereby lowering low-density lipoprotein cholesterol levels. A single dose of EpiReg-T delivered with lipid nanoparticles achieved efficient (>90%) and long-lasting (343 days) silencing of PCSK9 in the liver. Integrative multiomic analyses revealed minimal off-target effects in EpiReg-T-treated monkeys, mice and human-derived cells. EpiReg can be redirected to other genes by reengineering the DNA-binding domain. Our findings represent a step toward the clinical application of epigenetic editing for the treatment of human diseases.

Animals↗