Faculty Opinions recommendation of Regulation of selected genome loci using de novo-engineered transcription activator-like effector (TALE)-type transcription factors.

2010 ◽  
Author(s):  
Ian Henderson
Keyword(s):  
Transcription Factors ◽  
De Novo ◽  
Transcription Activator

Enhanced accumulation of pinosylvin stilbenes and related gene expression in Pinus strobus after infection of pine wood nematode

2021 ◽  
Author(s):  
Hwan-Su Hwang ◽  
Jung Yeon Han ◽  
Yong Eui Choi
Keyword(s):  
Transcription Factors ◽  
Defense Mechanisms ◽  
De Novo ◽  
Pinus Strobus ◽  
Pine Wilt Disease ◽  
Monomethyl Ether ◽  
Bursaphelenchus Xylophilus ◽  
Nematicidal Activity ◽  
Dependent Manner ◽  
Pine Wood

Abstract Pine wood nematodes (PWNs: Bursaphelenchus xylophilus) infect pine trees and cause serious pine wilt disease. Eastern white pine (Pinus strobus) has resistance to PWN. However, the detailed defense mechanisms of P. strobus against PWN are not well known. When P. strobus plants were infected with PWNs, the accumulation of stilbenoids, dihydropinosylvin monomethyl ether (DPME) and pinosylvin monomethyl ether (PME), were increased remarkably. DPME and PME had the high nematicidal activity. Interestingly, the nematicidal activity of the two compounds was resulted in a developmental stage-dependent manner. PME was more toxic to adult PWNs than juveniles, whereas DPME was found more toxic to juvenile PWNs than the adults. The genes involved in PME and DPME biosynthesis such as phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL), pinosylvin synthase (STS), and pinosylvin O-methyltransferase (PMT) were isolated using de novo sequencing of the transcriptome in P. strobus. In addition, transcription factors (bHLH, MYB and WRKY) related to stilbene biosynthesis were isolated. qPCR analyses of the selected genes (PAL, 4CL, STS, and PMT) including transcription factors (bHLH, MYB and WRKY) revealed that the expression level of the selected genes highly enhanced after PWN infection. Our results suggest that pinosylvin-type stilbenoid biosynthesis is highly responsive to PWN infection and plays an important role in PWN resistance of P. strobus trees.

A Novel Pathogenic Variant in the MN1 Gene in a Patient Presenting with Rhombencephalosynapsis and Craniofacial Anomalies, Expanding MN1 C-terminal Truncation Syndrome

2021 ◽  
Author(s):  
Carmen Palma ◽  
Pérez Mohand Patricia ◽  
José M. Lezana ◽  
Jaime Cruz ◽  
Juan F. Quesada ◽  
...  
Keyword(s):  
De Novo ◽  
Pathogenic Variant ◽  
Craniofacial Anomalies ◽  
Osteoblast Proliferation ◽  
Terminal Portion ◽  
Transcription Activator ◽  
Palate Development ◽  
Partial Rhombencephalosynapsis ◽  
And Function ◽  
Craniofacial Defects

AbstractMeningioma-1 is a transcription activator that regulates mammalian palate development and is required for appropriate osteoblast proliferation, motility, differentiation, and function. Microdeletions involving the MN1 gene have been linked to syndromes including craniofacial anomalies, such as Toriello–Carey syndrome. Recently, truncating variants in the C-terminal portion of the MN1 transcriptional factor have been linked to a characteristic and distinct phenotype presenting with craniofacial anomalies and partial rhombencephalosynapsis, a rare brain malformation characterized by midline fusion of the cerebellar hemispheres with partial or complete loss of the cerebellar vermis. It has been called MN1 C-terminal truncation (MCTT) syndrome or CEBALID (Craniofacial defects, dysmorphic Ears, Brain Abnormalities, Language delay, and Intellectual Disability) and suggested to be caused by dominantly acting truncated protein MN1 instead of haploinsufficiency. As a proto-oncogene, MN1 is also involved in familial meningioma. In this study, we present a novel case of MCTT syndrome in a female patient presenting with craniofacial anomalies and rhombencephalosynapsis, harboring a de novo pathogenic variant in the MN1 gene: c.3686_3698del, p.(Met1229Argfs*87).

scholarly journals Transcriptome analysis of Pueraria candollei var. mirifica for gene discovery in the biosyntheses of isoflavones and miroestrol

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Nithiwat Suntichaikamolkul ◽  
Kittitya Tantisuwanichkul ◽  
Pinidphon Prombutara ◽  
Khwanlada Kobtrakul ◽  
Julie Zumsteg ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Transcriptome Analysis ◽  
De Novo ◽  
Biosynthetic Genes ◽  
Pueraria Candollei ◽  
Isoflavone Synthase ◽  
Young Leaves ◽  
Plausible Mechanism ◽  
Polymerase Chain ◽  
R2r3 Myb

Abstract Background Pueraria candollei var. mirifica, a Thai medicinal plant used traditionally as a rejuvenating herb, is known as a rich source of phytoestrogens, including isoflavonoids and the highly estrogenic miroestrol and deoxymiroestrol. Although these active constituents in P. candollei var. mirifica have been known for some time, actual knowledge regarding their biosynthetic genes remains unknown. Results Miroestrol biosynthesis was reconsidered and the most plausible mechanism starting from the isoflavonoid daidzein was proposed. A de novo transcriptome analysis was conducted using combined P. candollei var. mirifica tissues of young leaves, mature leaves, tuberous cortices, and cortex-excised tubers. A total of 166,923 contigs was assembled for functional annotation using protein databases and as a library for identification of genes that are potentially involved in the biosynthesis of isoflavonoids and miroestrol. Twenty-one differentially expressed genes from four separate libraries were identified as candidates involved in these biosynthetic pathways, and their respective expressions were validated by quantitative real-time reverse transcription polymerase chain reaction. Notably, isoflavonoid and miroestrol profiling generated by LC-MS/MS was positively correlated with expression levels of isoflavonoid biosynthetic genes across the four types of tissues. Moreover, we identified R2R3 MYB transcription factors that may be involved in the regulation of isoflavonoid biosynthesis in P. candollei var. mirifica. To confirm the function of a key-isoflavone biosynthetic gene, P. candollei var. mirifica isoflavone synthase identified in our library was transiently co-expressed with an Arabidopsis MYB12 transcription factor (AtMYB12) in Nicotiana benthamiana leaves. Remarkably, the combined expression of these proteins led to the production of the isoflavone genistein. Conclusions Our results provide compelling evidence regarding the integration of transcriptome and metabolome as a powerful tool for identifying biosynthetic genes and transcription factors possibly involved in the isoflavonoid and miroestrol biosyntheses in P. candollei var. mirifica.

scholarly journals Dynamic epigenetic enhancer signatures reveal key transcription factors associated with monocytic differentiation states

Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. e161-e171 ◽  
Author(s):  
Thu-Hang Pham ◽  
Christopher Benner ◽  
Monika Lichtinger ◽  
Lucia Schwarzfischer ◽  
Yuhui Hu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
De Novo ◽  
Histone H3 ◽  
Human Macrophage ◽  
Cell Type ◽  
Monocytic Differentiation ◽  
Hematopoietic Stem ◽  
Chip Sequencing ◽  
Monocytes And Macrophages ◽  
Cell Type Specific

Abstract Cellular differentiation is orchestrated by lineage-specific transcription factors and associated with cell type–specific epigenetic signatures. In the present study, we used stage-specific, epigenetic “fingerprints” to deduce key transcriptional regulators of the human monocytic differentiation process. We globally mapped the distribution of epigenetic enhancer marks (histone H3 lysine 4 monomethylation, histone H3 lysine 27 acetylation, and the histone variant H2AZ), describe general properties of marked regions, and show that cell type–specific epigenetic “fingerprints” are correlated with specific, de novo–derived motif signatures at all of the differentiation stages studied (ie, hematopoietic stem cells, monocytes, and macrophages). We validated the novel, de novo–derived, macrophage-specific enhancer signature, which included ETS, CEBP, bZIP, EGR, E-Box and NF-κB motifs, by ChIP sequencing for a subset of motif corresponding transcription factors (PU.1, C/EBPβ, and EGR2), confirming their association with differentiation-associated epigenetic changes. We describe herein the dynamic enhancer landscape of human macrophage differentiation, highlight the power of genome-wide epigenetic profiling studies to reveal novel functional insights, and provide a unique resource for macrophage biologists.

scholarly journals Epstein-Barr Virus Nuclear Antigen Leader Protein Coactivates EP300

2018 ◽  
Vol 92 (9) ◽  
Author(s):  
Chong Wang ◽  
Hufeng Zhou ◽  
Yong Xue ◽  
Jun Liang ◽  
Yohei Narita ◽  
...  
Keyword(s):  
Transcription Factors ◽  
B Cells ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Transcription Activator ◽  
Lymphoproliferative Diseases ◽  
Barr Virus ◽  
Leader Protein ◽  
Epstein Barr

ABSTRACTEpstein-Barr virus nuclear antigen (EBNA) leader protein (EBNALP) is one of the first viral genes expressed upon B-cell infection. EBNALP is essential for EBV-mediated B-cell immortalization. EBNALP is thought to function primarily by coactivating EBNA2-mediated transcription. Chromatin immune precipitation followed by deep sequencing (ChIP-seq) studies highlight that EBNALP frequently cooccupies DNA sites with host cell transcription factors (TFs), in particular, EP300, implicating a broader role in transcription regulation. In this study, we investigated the mechanisms of EBNALP transcription coactivation through EP300. EBNALP greatly enhanced EP300 transcription activation when EP300 was tethered to a promoter. EBNALP coimmunoprecipitated endogenous EP300 from lymphoblastoid cell lines (LCLs). EBNALP W repeat serine residues 34, 36, and 63 were required for EP300 association and coactivation. Deletion of the EP300 histone acetyltransferase (HAT) domain greatly reduced EBNALP coactivation and abolished the EBNALP association. An EP300 bromodomain inhibitor also abolished EBNALP coactivation and blocked the EP300 association with EBNALP. EBNALP sites cooccupied by EP300 had significantly higher ChIP-seq signals for sequence-specific TFs, including SPI1, RelA, EBF1, IRF4, BATF, and PAX5. EBNALP- and EP300-cooccurring sites also had much higher H3K4me1 and H3K27ac signals, indicative of activated enhancers. EBNALP-only sites had much higher signals for DNA looping factors, including CTCF and RAD21. EBNALP coactivated reporters under the control of NF-κB or SPI1. EP300 inhibition abolished EBNALP coactivation of these reporters. Clustered regularly interspaced short palindromic repeat interference targeting of EBNALP enhancer sites significantly reduced target gene expression, including that of EP300 itself. These data suggest a previously unrecognized mechanism by which EBNALP coactivates transcription through subverting of EP300 and thus affects the expression of LCL genes regulated by a broad range of host TFs.IMPORTANCEEpstein-Barr virus was the first human DNA tumor virus discovered over 50 years ago. EBV is causally linked to ∼200,000 human malignancies annually. These cancers include endemic Burkitt lymphoma, Hodgkin lymphoma, lymphoma/lymphoproliferative disease in transplant recipients or HIV-infected people, nasopharyngeal carcinoma, and ∼10% of gastric carcinoma cases. EBV-immortalized human B cells faithfully model key aspects of EBV lymphoproliferative diseases and are useful models of EBV oncogenesis. EBNALP is essential for EBV to transform B cells and transcriptionally coactivates EBNA2 by removing repressors from EBNA2-bound DNA sites. Here, we found that EBNALP can also modulate the activity of the key transcription activator EP300, an acetyltransferase that activates a broad range of transcription factors. Our data suggest that EBNALP regulates a much broader range of host genes than was previously appreciated. A small-molecule inhibitor of EP300 abolished EBNALP coactivation of multiple target genes. These findings suggest novel therapeutic approaches to control EBV-associated lymphoproliferative diseases.

A Decade Decoded: Spies and Hackers in the History of TAL Effectors Research

2019 ◽  
Vol 57 (1) ◽  
pp. 459-481 ◽  
Author(s):  
Alvaro L. Perez-Quintero ◽  
Boris Szurek
Keyword(s):  
Transcription Factors ◽  
Current Knowledge ◽  
Bacterial Colonization ◽  
Binding Mechanism ◽  
Transcription Activator ◽  
Plant Host ◽  
Tal Effectors ◽  
Specific Amino Acid ◽  
History Of ◽  
Weak Points

Transcription activator-like effectors (TALEs) from the genus Xanthomonas are proteins with the remarkable ability to directly bind the promoters of genes in the plant host to induce their expression, which often helps bacterial colonization. Metaphorically, TALEs act as spies that infiltrate the plant disguised as high-ranking civilians (transcription factors) to trick the plant into activating weak points that allow an invasion. Current knowledge of how TALEs operate allows researchers to predict their activity (counterespionage) and exploit their function, engineering them to do our bidding (a Manchurian agent). This has been possible thanks particularly to the discovery of their DNA binding mechanism, which obeys specific amino acid–DNA correspondences (the TALE code). Here, we review the history of how researchers discovered the way these proteins work and what has changed in the ten years since the discovery of the code. Recommended music for reading this review can be found in the Supplemental Material .

scholarly journals NFκB dynamics determine the stimulus-specificity of epigenomic reprogramming in macrophages

2020 ◽  
Author(s):  
Quen J. Cheng ◽  
Sho Ohta ◽  
Katherine M. Sheu ◽  
Roberto Spreafico ◽  
Adewunmi Adelaja ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Temporal Dynamics ◽  
De Novo ◽  
Innate Immune ◽  
Open Chromatin ◽  
Specific Memory ◽  
Genetic Perturbations ◽  
Expression Potential ◽  
Epigenomic Reprogramming ◽  
Light Chain Enhancer

SummaryThe epigenome defines the cell type, but also shows plasticity that enables cells to tune their gene expression potential to the context of extracellular cues. This is evident in immune sentinel cells such as macrophages, which can respond to pathogens and cytokines with phenotypic shifts that are driven by epigenomic reprogramming1. Recent studies indicate that this reprogramming arises from the activity of transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), which binds not only to available enhancers but may produce de novo enhancers in previously silent areas of the genome2. Here, we show that NFκB reprograms the macrophage epigenome in a stimulus-specific manner, in response only to a subset of pathogen-derived stimuli. The basis for these surprising differences lies in the stimulus-specific temporal dynamics of NFκB activity. Testing predictions of a mathematical model of nucleosome interactions, we demonstrate through live cell imaging and genetic perturbations that NFκB promotes open chromatin and formation of de novo enhancers most strongly when its activity is non-oscillatory. These de novo enhancers result in the activation of additional response genes. Our study demonstrates that the temporal dynamics of NFκB activity, which encode ligand identity3, can be decoded by the epigenome through de novo enhancer formation. We propose a mechanistic paradigm in which the temporal dynamics of transcription factors are a key determinant of their capacity to control epigenomic reprogramming, thus enabling the formation of stimulus-specific memory in innate immune sentinel cells.

scholarly journals Transcriptome analysis of immature xylem in Chinese fir at different developmental phases

2016 ◽  
Author(s):  
Yunxing Zhang ◽  
Xiaojiao Han ◽  
Jian Sang ◽  
Xuelian he ◽  
Mingying Liu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Transcriptome Sequencing ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Southern China ◽  
Wood Formation ◽  
Chinese Fir ◽  
Nac Transcription Factors ◽  
Transcriptome Variation ◽  
Developmental Phases

Background: Chinese fir [Cunninghamia lanceolata (Lamb .) Hook.], is one of the most important native tree species for timber production in southern China. An understanding of overall fast growing stage, stem growth stage and senescence stage cambium transcriptome variation is lacking. We used transcriptome sequencing to identify the repertoire of genes expressed during development of xylem tissue in Chinese fir, aiming to delineate the molecular mechanisms of wood formation. Results: We carried out transcriptome sequencing at three different cultivation ages (7Y, 15Y and 21Y) generating 68.71 million reads (13.88 Gbp). A total of 140,486 unigenes with a mean size of 568.64 base pairs (bp) were obtained via de novo assembly. Of these, 27,427 unigenes (19.52%) were further annotated by comparison to public protein databases. A total of 5,331 (3.79%) unigenes were mapped into 118 pathways by searching against the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG). Differentially expressed genes (DEG) analysis identified 3, 16 and 5,899 DEGs from the comparison of 7Y vs. 15Y, 7Y vs. 21Y and 15Y vs. 21Y, respectively, in the immature xylem tissues, including 2,638 significantly up-regulated and 3,280 significantly down-regulated genes. Besides, five NAC transcription factors, 190 MYB transcription factors, and 34 WRKY transcription factors were identified respectively from Chinese fir transcriptome. Conclusion: Our results revealed the active transcriptional pathways and identified the DEGs at different cultivation phases of Chinese fir wood formation. This transcriptome dataset will aid in understanding and carrying out future studies on the molecular basis of Chinese fir wood formation and contribute to future artificial production and applications.

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