44 results about "Transcriptional repression" patented technology

The invention discloses application of a TaLBD30 protein and a coding gene thereof in regulating and controlling a wheat plant type. The invention belongs to the technical field of biology, and particularly relates to application of TaLBD30 protein and a coding gene thereof to regulation and control of wheat plant types. The protein is any one of the following proteins: A1) a protein with an amino acid sequence as shown in SEQ ID No: 1; a2) a protein which is obtained by substitution and / or deletion and / or addition of amino acid residues on the protein of A1), has 80% or more of identity with the protein of A1) and has the same function as the protein of A1); a3) a fusion protein obtained by connecting a protein tag to the N terminal or / and the C terminal of A1) or A2). TaLBD30 is a transcription factor with transcription inhibition activity, and compared with a wild type, the TaLBD30 gene overexpression shows that after TaLBD30 overexpression, the wheat plant height and ear length are remarkably reduced.

The present invention relates generally to compositions, systems and methods for modulating hepatitis B virus (HBV) by targeting gene repression. In particular, the present invention provides an epigenetically modified DNA targeting system, such as a CRISPR-Cas / guide RNA (gRNA) system, for transcriptional repression of hepatitis B virus genes to promote cell phenotypes that lead to reduced HBV infection. In some embodiments, the epigenetically modified DNA targeting systems of the present invention bind to or target a target site of at least one gene in the hepatitis B virus DNA sequence or a regulatory element thereof in a cell. In some aspects, the systems provided herein relate to transcriptional repression of one or more hepatitis B virus genes and / or regulatory elements thereof. In some aspects, the invention also provides methods and uses associated with the provided compositions, such as in repression of hepatitis B virus replication and expression associated with hepatitis B infection.

The invention discloses an application of an activator combined by one or more genes / proteins in preparation of drugs for treating hypertrophic scars, and belongs to the technical field of biological medicines. In order to solve the problem that when retinoic acid cream is used for preparing hypertrophic scars, a specific mode and an action target of a retinoic acid signal channel for regulating and controlling fibroblasts are not disclosed yet, the action target and a regulation and control mechanism of ATRA for regulating and controlling fibroblast activation and glucose metabolism remodeling are explored through in-vivo and in-vitro experiments; and on the basis of a Cre-loxP system, the function of the target gene is verified. Researches in the invention show that ATRA promotes transcription of HIC1 and inhibits transcription and expression of TGF-beta1 by activating RAR alpha on one hand, and ATRA promotes transcription of HIC1 and inhibits transcription and expression of TGF-beta1 on the other hand; on the other hand, the transcription of PCK1 and PCK2 is promoted, so that the proliferation and abnormal activation of HSFs are reduced, and the occurrence and development processes of hypertrophic scars are finally inhibited. The conclusion provides a sufficient theoretical basis for inhibiting hypertrophic scar formation by ATRA.

A complex comprising a first fusion and a second fusion, wherein one of the first fusion and the second fusion comprises a DNA methylation domain and at least one recruitment domain A, and the other fusion comprises a transcriptional repressor domain and at least one recruitment domain A', wherein the recruitment domain A and the recruitment domain A' are capable of interacting with each other such that one of the first fusion and the second fusion, or a portion thereof, can be recruited to the vicinity of the other fusion. Further provided is the use of the complex in the manufacture of a product for silencing expression of a target gene and in the manufacture of a medicament.

A clustered regularly interspaced short palindromic repeat (CRISPR)-associated complex for adaptive antiviral defence (Cascade); the Cascade protein complex comprising at least CRISPR-associated protein subunits Cas7, Cas5 and Cas6 which includes at least one subunit with an additional amino acid sequence possessing nucleic acid or chromatin modifying, visualising, transcription activating or transcription repressing activity. The Cascade complex with additional activity is combined with an RNA molecule to produce a ribonucleoprotein complex. The RNA molecule is selected to have substantial complementarity to a target sequence. Targeted ribonucleoproteins can be used as genetic engineering tools for precise cutting of nucleic acids in homologous recombination, non-homologous end joining, gene modification, gene integration, mutation repair or for their visualisation, transcriptional activation or repression. A pair of ribonucleotides fused to FokI dimers may be used to generate double-strand breakages in the DNA to facilitate these applications in a sequence-specific manner.

The application discloses high-temperature-resistant engineered methanotrophs with high glutamic acid yield, a construction method and application thereof, and belongs to the field of industrial biotechnology. Methylotuvimicrobium buryatense 5GB1 as the host strain, transcriptional inhibition of the SOS response system by LexA protein is removed by knocking out a lexA gene in the genome of the host strain, expression of DNA damage repair related genes in the cell is activated, and high-temperature-resistant engineered methanotrophs MBΔ lexA that can stably grow in a high-temperature environment of 40-45 DEG C are obtained. The strain can still maintain normal growth and metabolism with methane as the sole carbon source under the condition of 40-45 DEG C, and the glutamic acid synthesis capacity of the strain is significantly better than that of the original strain at normal temperature. The high-temperature-resistant engineered methanotrophs MBΔ lexA provide important strain resources for the production of amino acid products by methanotroph cell factories in a high-temperature industrial scene, and are expected to improve the economy and sustainability of methanotrophic bioconversion.

This invention belongs to the field of plant molecular biology and genetic breeding technology, specifically relating to a molecular marker related to the malic acid content of apple fruit and its application. The molecular marker is... MdNAC029 The single nucleotide polymorphism site in the gene promoter region, this site is located MdNAC029 The nucleotide sequence of the gene promoter region, starting from the 2693rd base at the 5' end, corresponds to... MdNAC029 At a position 442 bp upstream of the transcription start codon, the polymorphism is either T or C, with the C / C genotype indicating high malic acid content and the T / T genotype indicating low malic acid content. This invention, through molecular biology experiments, confirms that the T allele is the binding site for the transcriptional repressor MdMYC2, and the C allele eliminates the binding of MdMYC2, thereby relieving transcriptional repression and promoting malic acid accumulation. This provides a new molecular marker for the genetic improvement of apple fruit acidity traits, accelerating the breeding process of superior varieties.

Provided herein are epigenetic-modifying DNA-targeting systems, such as CRISPR-Cas / guide RNA (gRNA) systems, for the transcriptional repression of Hepatitis B viral (HBV) genes to promote a cellular phenotype that leads to the reduction of HBV infection. In some embodiments, the epigenetic-modifying DNA-targeting systems bind to or target a target site of at least one gene or regulatory element thereof in a Hepatitis B viral DNA sequence in cell. In some aspects, the provided systems relate to the transcriptional repression of one or more Hepatitis B viral gene and / or regulatory element thereof. In some aspects, also provided herein are methods and uses related to the provided compositions, for example in repressing Hepatitis B viral replication and expression in connection with Hepatitis B infections.

Provided herein are epigenetic-modifying DNA-targeting systems, such as CRISPR-Cas / guide RNA (gRNA) systems, for the transcriptional repression of Hepatitis B viral (HBV) genes to promote a cellular phenotype that leads to the reduction of HBV infection. In some embodiments, the epigenetic-modifying DNA-targeting systems bind to or target a target site of at least one gene or regulatory element thereof in a Hepatitis B viral DNA sequence in cell. In some aspects, the provided systems relate to the transcriptional repression of one or more Hepatitis B viral gene and / or regulatory element thereof. In some aspects, also provided herein are methods and uses related to the provided compositions, for example in repressing Hepatitis B viral replication and expression in connection with Hepatitis B infections.

The application discloses a kind of preeclampsia (Preeclampsia, PE) diagnosis and treatment biology marker and its application;The application is from clinical sample, cell and in-depth demonstration of overexpressed FBP2 at the level of body, which causes the mechanism of PE occurrence by inhibiting the invasion of trophoblasts, and the application verifies that the classic gene HEY1 downstream of NOTCH3 can be combined with the promoter region of FBP2 and transcribe to inhibit the expression of FBP2, FBP2 is combined with c-MYC protein and inhibits the transcriptional activity of c-MYC, down-regulates the transcriptional expression of TFAM, causes mitochondrial dysfunction, weakens the migration and invasion ability of trophoblasts, participates in the mechanism of PE occurrence, is a new mechanism clue obtained according to the results of pre-experiment and information analysis, is a new target for in-depth exploration of PE clinical diagnosis and treatment, and the research results can provide theoretical basis for guiding early prediction and intervention of PE in the future.

Disclosed herein are Type I Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) / CRISPR-associated (Cas) programmable systems and methods of using said Type I CRISPR / Cas programmable systems for activating gene expression, repressing gene expression, and gene editing. The disclosure relates to compositions that include Type I CRISPR-Cas fusion proteins designed for transcriptional activation, transcriptional repression, and / or gene editing of target genes in eukaryotic cells. The disclosure relates to Type I Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) / CRISPR-associated (Cas) transcriptional activation system related compositions and methods of using said Type I CRISPR / Cas transcriptional activation system related compositions for activating gene expression. The disclosure relates to compositions that include a Type I CRISPR-Cas fusion protein designed for transcriptional activation of target genes in eukaryotic cells.

According to the application of the rosiglitazone in preparation of the medicine for treating the glioma and the composition of the rosiglitazone, a brand-new Rb-E2F1-mediated MND1 transcription inhibition mechanism of the rosiglitazone in the glioma is clarified for the first time; and a new strategy with a great transformation prospect is provided for treatment of glioma, namely, a clinical drug rosiglitazone which has been subjected to security certification is utilized to interfere DNA repair steady state of glioma cells through targeted inhibition of MND1, so that tumor growth is inhibited.

The present invention relates to the use of an inhibitor of UHRF1 in the preparation of a medicament for treating tissue fibrosis after spinal cord injury, belonging to the technical field of biomedicine. The present invention has confirmed that spinal cord injury can lead to an increase in the expression of UHRF1; compared with the mice in the sham operation group, the mice with specific knockdown of UHRF1 in fibroblasts significantly reduced the fibrosis caused by spinal cord injury and promoted nerve regeneration, and the motor function was significantly improved. In terms of mechanism, the knockdown of UHRF1 led to a decrease in the number of its proteins bound to the promoter of the PPM1A gene, resulting in a weakened transcriptional inhibitory effect, promoting the expression of the PPM1A gene, and PPM1A can inhibit the phosphorylation of Smad2 / 3 and inhibit the conduction of the TGF-β1 / Smads pathway, thereby inhibiting tissue fibrosis.

The present application relates to an engineered gene transcriptional repression tool and a use thereof, in particular to an epigenetic editor, comprising a transcription activator-like effector (TALE) domain, at least one epigenetic modification domain, and at least one transcriptional regulatory domain, wherein the domains can be directly or indirectly linked; or the domains form various fusions and interact by means of recruitment.

Provided is an epigenetic editor comprising a transcriptional activator-like effector (TALE) domain, at least one epigenetic modification domain, and at least one transcriptional regulatory domain; wherein the TALE domain can be specifically combined with a target nucleotide sequence on an HBV (Hepatitis B Virus) gene and / or a regulatory element of the HBV gene.

The application discloses TaLBD30 protein and an application of a coding gene thereof in regulating a wheat plant type, and belongs to the technical field of biotechnology, and particularly relates to the application of the TaLBD30 protein and the coding gene thereof in regulating the wheat plant type. The protein is any one of the following: A1) a protein with an amino acid sequence as shown in SEQ ID No:1; A2) a protein obtained by substitution, deletion and / or addition of amino acid residues on the protein of A1), the protein being identical to the protein shown in A1) by more than 80% and having the same function; and A3) a fusion protein obtained by connecting a protein tag to the N terminal or / and C terminal of A1) or A2). The TaLBD30 is a transcription factor with transcription inhibition activity, and when overexpressed TaLBD30 , the wheat plant height and ear length are significantly reduced compared with a wild type. TaLBD30 ​

Provided herein are epigenetic-modifying DNA-targeting systems, such as CRISPR-Cas / guide RNA (gRNA) systems, for the transcriptional repression of Hepatitis B viral (HBV) genes to promote a cellular phenotype that leads to the reduction of HBV infection. In some embodiments, the epigenetic-modifying DNA-targeting systems bind to or target a target site of at least one gene or regulatory element thereof in a Hepatitis B viral DNA sequence in cell. In some aspects, the provided systems relate to the transcriptional repression of one or more Hepatitis B viral gene and / or regulatory element thereof. In some aspects, also provided herein are methods and uses related to the provided compositions, for example in repressing Hepatitis B viral replication and expression in connection with Hepatitis B infections.

The present invention provides a chromatin-derived genes transcriptional signature suitable to classify two subgroups of prostate cancer patients with different BCR outcome. Gene expression analysis revealed a protective, antitumoral activity of the HDD subtype associated with changes in chromatin compartments and transcriptional repression. The transcriptional signature of the invention confirmed its prognostic relevance across multiple cohorts covering more than 900 prostate cancer patients in total thus providing an innovative strategy for the stratification of primary prostate cancers.

This invention discloses a MYB transcriptional repressor, AsMYB054, related to the synthesis of 2-(2-phenylethyl) chromones in Aquilaria sinensis and its applications. Targeting the weak links in the synthesis and regulation of 2-(2-phenylethyl) chromone compounds, this invention clones for the first time the AsMYB054 gene, a transcriptional repressor related to the regulation of 2-(2-phenylethyl) chromone synthesis in Aquilaria sinensis. AsMYB054 is located in the cell nucleus and possesses transcriptional repressive activity, capable of binding to and inhibiting the activity of the promoters of enzyme genes AsPKS02 and AsPKS09, which are related to the biosynthesis of 2-(2-phenylethyl) chromone compounds. Inhibiting the expression of AsMYB054 using gene editing or RNA interference techniques can promote the accumulation of 2-(2-phenylethyl) chromone compounds in Aquilaria sinensis, showing broad application prospects and significant economic value.

Provided herein are compositions, systems, and methods for the generation, identification, and characterization of effector domains for activating and silencing gene expression. In particular, synthetic transcription factors comprising one or more transcriptional activator domains, one or more transcriptional repressor domains, or a combination thereof fused to a heterologous DNA binding domain, and methods of using thereof are provided.

This invention relates to the application of an IGF-1R gene expression inhibitor in the preparation of drugs for delaying aging and improving age-related diseases. Using gene interference technology, siRNA targeting the IGF-1R gene is designed and chemically modified to inhibit its expression by suppressing transcription and downstream signaling pathways. Compared with middle-aged control mice, the hair condition, motor ability, and learning and memory functions of the middle-aged mice were significantly improved under IGF-1R inhibition, even resembling those of adult mice. This indicates that the IGF-1R gene is an important factor in delaying aging. Therefore, designing drugs that inhibit IGF-1R expression can provide a new direction for the development of anti-aging and age-related disease prevention drugs, showing great promise for anti-aging target applications.

The present application relates to an engineered gene transcriptional repression tool targeting inhibin subunit βE (INHBE) and the use thereof, and specifically relates to a complex comprising a first fusion and a second fusion, wherein: 1) one of the first fusion and the second fusion comprises a DNA methylation domain and at least one recruitment domain A, and the other fusion comprises a transcriptional repressor domain and at least one recruitment domain A'; and 2) the first fusion or the second fusion comprises a nucleic acid-binding domain. Moreover, the recruitment domain A and the recruitment domain A' are capable of interacting with each other, such that one of the first fusion and the second fusion or a part thereof can be recruited to the vicinity of the other fusion; and the nucleic acid-binding domain is capable of specifically binding to an INHBE gene transcriptional regulatory element.

This invention discloses the application of the NbMYB159 gene in the positive regulation of the MVA metabolic pathway in Nicotiana benthamiana, belonging to the field of genetic engineering technology. The technical solution includes the application of the NbMYB159 gene in the positive regulation of the MVA metabolic pathway in Nicotiana benthamiana. The nucleotide sequence of the gene is shown in SEQ ID NO: 1. The NbMYB159 gene can enhance the metabolic flux of the MVA pathway by activating the expression of key structural genes in the Nicotiana benthamiana MVA pathway. This invention discovers that NbMYB159 can specifically bind to the promoter regions of NbHMGR and NbHMGS, activating the expression of all genes in the MVA pathway. Transient overexpression of NbMYB159 in Nicotiana benthamiana significantly increases the content of endogenous FPP in Nicotiana benthamiana. Stable overexpression lines significantly increase the content of endogenous FPP in Nicotiana benthamiana without affecting the biomass of Nicotiana benthamiana, while transcriptional repression overexpression lines significantly reduce the content of FPP. This discovery is of great significance for the engineering modification of the Nicotiana benthamiana chassis and can effectively solve the problem of low production efficiency of sesquiterpenes and triterpenes in Nicotiana benthamiana.

The invention discloses application of a BHLHE22 gene in triple negative breast cancer, and belongs to the technical field of biological medicines. Data analysis shows that in triple negative breast cancer (TNBC), the expression of the BHLHE22 gene is reduced, and the low expression of the BHLHE22 gene is related to advanced pathological staging and poor prognosis. Meanwhile, experiments show that overexpression of the BHLHE22 can inhibit growth of tumor cells, and silence of the gene can promote malignant progression. Meanwhile, the deubiquitination enzyme OTUD3 stabilizes the BHLHE22 protein through the deubiquitination activity of the deubiquitination enzyme OTUD3, and the effect depends on the key C76 site of the deubiquitination enzyme OTUD3. In addition, the BHLHE22 inhibits a downstream target gene CDT1 through transcription to play an anti-proliferation function, and the effect can be reversed by CDT1 overexpression. The invention discloses the key cancer suppression effect of the OTUD3 / BHLHE22 / CDT1 signal axis in the TNBC, and provides a new potential target spot for the diagnosis and treatment of the TNBC.

This invention relates to a method based on argB A method for constructing a high-arginine-producing genetically engineered strain using mutants, and the application of this genetically engineered strain in the microbial fermentation production of arginine. The genetically engineered strain was obtained by performing the following gene editing on its genome, starting with Corynebacterium glutamicum ATCC 13032; this invention first involves knocking out the gene encoding the arginine biosynthesis repressor protein. argR and last Relieve transcriptional repression; knock out the gene encoding glutamate kinase. proB Blocking the competitive pathway for the synthesis of the byproduct L-proline; knocking out global nitrogen metabolism regulators. amtR To relieve nitrogen metabolism restriction and enhance nitrogen source supply; to knock out the gene encoding the mechanosensitive channel protein. yggB By altering cell membrane permeability and reducing the leakage of byproducts (such as glutamate), it indirectly promotes arginine accumulation; based on the knockout of the original proB, ldh Replace with Ptac- argB *(T94S, I158V, R273K) strains were constructed to reduce lactic acid byproducts while resisting feedback inhibition; finally, the L-arginine exporter gene was overexpressed via plasmid. lysE By combining the above modification strategies, a genetically engineered strain ARG6-Ptac-, which produces high levels of arginine, was constructed. argB * / pXMJ19- lysE This engineered strain exhibits excellent L-arginine production capacity in both shake flask and fermenter scales (10.3 g / L in shake flask and 105.2 g / L in fed-batch fermentation), and its genetic traits are stable, making it suitable for industrial production.

Provided herein are epigenetic-modifying DNA-targeting systems, such as CRISPR-Cas / guide RNA (gRNA) systems, for the transcriptional repression of Hepatitis B viral (HBV) genes to promote a cellular phenotype that leads to the reduction of HBV infection. In some embodiments, the epigenetic-modifying DNA-targeting systems bind to or target a target site of at least one gene or regulatory element thereof in a Hepatitis B viral DNA sequence in cell. In some aspects, the provided systems relate to the transcriptional repression of one or more Hepatitis B viral gene and / or regulatory element thereof. In some aspects, also provided herein are methods and uses related to the provided compositions, for example in repressing Hepatitis B viral replication and expression in connection with Hepatitis B infections.

This invention discloses a rutin-containing composition and its applications, belonging to the field of drug development technology. Through molecular docking simulations, animal experiments, and cell experiments, this invention demonstrates that rutin exerts its detoxification effect through a dual mechanism: firstly, it antagonizes the inhibitory effect of α-amatoxins on RNA polymerase II, improving transcriptional repression induced by poisoning; secondly, it alleviates oxidative stress caused by α-amatoxins, reducing MDA content and increasing SOD activity. Rutin significantly improves the survival rate of mice poisoned by α-amatoxins, improves hepatocellular pathological damage, and reduces liver function indicators AST and ALT levels. The optimal dosage is 175 mg / kg, indicating that rutin can be considered a potential therapeutic drug for α-amatoxins poisoning. This invention provides a new treatment option for α-amatoxins poisoning. Rutin is a marketed drug with guaranteed safety and significant advantages for clinical translation.

The invention provides a transcription suppressor and application thereof, and finds that after the suppressor is knocked out, the expression quantity of a related target gene (LOCOs08g06320) in rice is obviously increased, which indicates that after the suppressor is knocked out, the expression of the target gene is relieved, the element is verified to have definite inhibitory activity on the transcriptional level, and in addition, the transcription suppressor can be used for preparing the rice transcription suppressor. The invention further provides a method for transferring the suppressor into a vector to artificially regulate and control the expression of related genes for the first time. The discovery provides a new research direction for crop breeding, and has important breeding significance and development prospects. Compared with the prior art, a gene with transcriptional inhibition activity is identified and verified for the first time, the inhibitor can be applied to yield regulation and stress response in follow-up research by utilizing the inhibition characteristic of the inhibitor, and the inhibitor can play an important role in the technical fields of follow-up molecular biology and crop genetic improvement. The obvious biological and application values are realized.

The present invention relates to an attenuated SARS-CoV-2 vaccine strain including nucleocapsid N gene transcriptional repression and a non-structural protein 1 (nsp1) protein mutation, and a use thereof. The attenuated SARS-CoV-2 vaccine strain according to the present invention has excellent safety and efficacy as a vaccine, and thus can be effectively used as an attenuated live vaccine for the prevention of coronavirus disease 2019.

The invention provides application of quercetin in preparation of a glioblastoma ferroptosis inducer, and belongs to the technical field of biological medicine. Human-derived glioblastoma U251 cells are used for an in-vitro experiment, and it is proved that in glioblastoma, quercetin can reduce transcription of FTH1 genes and GPX4 genes, promote transcription of TFR1 genes, inhibit expression of FTH1 protein and GPX4 protein, reduce the content of GSH, improve the content of MDA and the content of Fe < 2 + >, promote ferroptosis of the human-derived glioblastoma U251 cells, and can be used for preparing a medicine for treating the glioblastoma. The growth and migration of the plants can be obviously inhibited. The invention further provides a glioblastoma ferroptosis inducer based on quercetin as an active component and application of the glioblastoma ferroptosis inducer in preparation of drugs for preventing and / or treating glioblastoma.