scholarly journals Epigenetic manipulation of gene expression

2005 ◽  
Vol 169 (6) ◽  
pp. 847-857 ◽  
Author(s):  
Rudy L. Juliano ◽  
Vidula R. Dixit ◽  
Hyunmin Kang ◽  
Tai Young Kim ◽  
Yuko Miyamoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Culture ◽  
Gene Regulation ◽  
Transcription Factors ◽  
Rna Interference ◽  
Antisense Oligonucleotide ◽  
Significant Progress ◽  
Direct Experience ◽  
Key Features ◽  
Epigenetic Manipulation

Cell biologists have been afforded extraordinary new opportunities for experimentation by the emergence of powerful technologies that allow the selective manipulation of gene expression. Currently, RNA interference is very much in the limelight; however, significant progress has also been made with two other approaches. Thus, antisense oligonucleotide technology is undergoing a resurgence as a result of improvements in the chemistry of these molecules, whereas designed transcription factors offer a powerful and increasingly convenient strategy for either up- or down-regulation of targeted genes. This mini-review will highlight some of the key features of these three approaches to gene regulation, as well as provide pragmatic guidance concerning their use in cell biological experimentation based on our direct experience with each of these technologies. The approaches discussed here are being intensely pursued in terms of possible therapeutic applications. However, we will restrict our comments primarily to the cell culture situation, only briefly alluding to fundamental differences between utilization in animals versus cells.

scholarly journals The AML-associated K313 mutation enhances C/EBPα activity by leading to C/EBPα overexpression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ian Edward Gentle ◽  
Isabel Moelter ◽  
Mohamed Tarek Badr ◽  
Konstanze Döhner ◽  
Michael Lübbert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Culture ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Transcriptional Activity ◽  
Target Gene ◽  
Wild Type ◽  
Elevated Expression ◽  
Factor C ◽  
Acute Myeloid

AbstractMutations in the transcription factor C/EBPα are found in ~10% of all acute myeloid leukaemia (AML) cases but the contribution of these mutations to leukemogenesis is incompletely understood. We here use a mouse model of granulocyte progenitors expressing conditionally active HoxB8 to assess the cell biological and molecular activity of C/EBPα-mutations associated with human AML. Both N-terminal truncation and C-terminal AML-associated mutations of C/EBPα substantially altered differentiation of progenitors into mature neutrophils in cell culture. Closer analysis of the C/EBPα-K313-duplication showed expansion and prolonged survival of mutant C/EBPα-expressing granulocytes following adoptive transfer into mice. C/EBPα-protein containing the K313-mutation further showed strongly enhanced transcriptional activity compared with the wild-type protein at certain promoters. Analysis of differentially regulated genes in cells overexpressing C/EBPα-K313 indicates a strong correlation with genes regulated by C/EBPα. Analysis of transcription factor enrichment in the differentially regulated genes indicated a strong reliance of SPI1/PU.1, suggesting that despite reduced DNA binding, C/EBPα-K313 is active in regulating target gene expression and acts largely through a network of other transcription factors. Strikingly, the K313 mutation caused strongly elevated expression of C/EBPα-protein, which could also be seen in primary K313 mutated AML blasts, explaining the enhanced C/EBPα activity in K313-expressing cells.

scholarly journals Regulation and imaging of gene expression via an RNA interference antagonistic biomimetic probe

2017 ◽  
Vol 8 (7) ◽  
pp. 4973-4977 ◽  
Author(s):  
Kai Zhang ◽  
Xue-Jiao Yang ◽  
Wei Zhao ◽  
Ming-Chen Xu ◽  
Jing-Juan Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Rna Interference ◽  
Living Cells

A versatile strategy is reported which permits gene regulation and imaging in living cells via an RNA interference antagonistic probe.

Gene regulation through chromatin remodelling by members of the nuclear receptor superfamily

2000 ◽  
Vol 28 (4) ◽  
pp. 369-373 ◽  
Author(s):  
I. J. McEwan
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transcription Factors ◽  
Thyroid Hormones ◽  
Target Gene ◽  
Protein Complexes ◽  
Nuclear Receptor Superfamily ◽  
Target Gene Expression ◽  
Dna Elements ◽  
Introductory Review

The intracellular receptors for steroid hormones, thyroid hormones, retinoids and vitamin D3 are known to bind to specific DNA elements and thus regulate target gene expression. This introductory review and the following papers address some of the mechanisms underlying this action. In particular, the ability of this family of transcription factors to recruit multi-protein complexes that have the capacity to remodel chromatin structure in order to silence or activate target gene expression is discussed.

scholarly journals DNA accessibility is not the primary determinant of chromatin-mediated gene regulation

2019 ◽  
Author(s):  
Răzvan V. Chereji ◽  
Peter R. Eriksson ◽  
Josefina Ocampo ◽  
David J. Clark
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transcription Factors ◽  
Restriction Enzyme ◽  
Chromatin Structure ◽  
Mouse Liver ◽  
Digestion Rate ◽  
Dna Accessibility ◽  
Primary Determinant ◽  
Liver Nuclei

ABSTRACTDNA accessibility is thought to be of major importance in regulating gene expression. We test this hypothesis using a restriction enzyme as a probe of chromatin structure and as a proxy for transcription factors. We measured the digestion rate and the fraction of accessible DNA at all genomicAluI sites in budding yeast and mouse liver nuclei. Hepatocyte DNA is more accessible than yeast DNA, consistent with longer linkers between nucleosomes, and indicating that nucleosome spacing is a major determinant of accessibility. DNA accessibility varies from cell to cell, such that essentially no sites are accessible or inaccessible in every cell.AluI sites in inactive mouse promoters are accessible in some cells, implying that transcription factors could bind without activating the gene. Euchromatin and heterochromatin have very similar accessibilities, suggesting that transcription factors can penetrate heterochromatin. Thus, DNA accessibility is not likely to be the primary determinant of gene regulation.

scholarly journals Endogenous BioID elucidates TCF7L1 interactome modulation upon GSK-3 inhibition in mouse ESCs

2018 ◽  
Author(s):  
Steven Moreira ◽  
Caleb Seo ◽  
Victor Gordon ◽  
Sansi Xing ◽  
Ruilin Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transcription Factors ◽  
Target Gene ◽  
Single Copy ◽  
List Type ◽  
Interacting Proteins ◽  
Mouse Escs ◽  
Biotin Ligase ◽  
Biotin Labeling

Modulation of Wnt target gene expression via the TCF/LEFs remains poorly understood. We employ proximity-based biotin labeling (BioID) to examine GSK-3 inhibitor effects on the TCF7L1 interactome in mouse ESCs. We generated ESC lines with biotin ligase BirA* fused to TCF7L1 by knocking it into the endogenous TCF7L1 locus or by inserting a doxinducible BirA*-TCF7L1 transgene into the Rosa26 locus. Induction yielded BirA*-TCF7L1 levels 3-fold higher than in the endogenous system, but substantial overlap in biotinylated proteins with high peptide counts were detected by each method. Known TCF7L1 interactors TLE3/4 and β-catenin, and numerous proteins not previously associated with TCF7L1, were identified in both systems. Despite reduced BirA*-TCF7L1 levels, the number of hits identified with both BioID approaches increased after GSK-3 inhibition. We elucidate the network of TCF7L1 proximal proteins regulated by GSK-3 inhibition, validate the utility of endogenous BioID, and provide mechanistic insights into TCF7L1 target gene regulation.HighlightsBirA*-TCF7L1 at single-copy physiological levels generates robust BioID dataCHIR99021 reduces TCF7L1 levels but increases detectable TCF7L1-proximal proteinsThe TCF7L1 interactome of largely epigenetic/transcription factors fluctuates with GSK-3 inhibitionJMJD1C, SALL4 and BRG1/SMARCA4 are validated as TCF7L-interacting proteins

scholarly journals Biological signal processing filters via engineering allosteric transcription factors

2021 ◽  
Vol 118 (46) ◽  
pp. e2111450118
Author(s):  
Thomas M. Groseclose ◽  
Ashley N. Hersey ◽  
Brian D. Huang ◽  
Matthew J. Realff ◽  
Corey J. Wilson
Keyword(s):  
Gene Expression ◽  
Signal Processing ◽  
Gene Regulation ◽  
Transcription Factors ◽  
Input Signal ◽  
Kinetic Studies ◽  
Lactose Repressor ◽  
Biological Signal ◽  
Biological Signal Processing ◽  
Biological Phenomena

Signal processing is critical to a myriad of biological phenomena (natural and engineered) that involve gene regulation. Biological signal processing can be achieved by way of allosteric transcription factors. In canonical regulatory systems (e.g., the lactose repressor), an INPUT signal results in the induction of a given transcription factor and objectively switches gene expression from an OFF state to an ON state. In such biological systems, to revert the gene expression back to the OFF state requires the aggressive dilution of the input signal, which can take 1 or more d to achieve in a typical biotic system. In this study, we present a class of engineered allosteric transcription factors capable of processing two-signal INPUTS, such that a sequence of INPUTS can rapidly transition gene expression between alternating OFF and ON states. Here, we present two fundamental biological signal processing filters, BANDPASS and BANDSTOP, that are regulated by D-fucose and isopropyl-β-D-1-thiogalactopyranoside. BANDPASS signal processing filters facilitate OFF–ON–OFF gene regulation. Whereas, BANDSTOP filters facilitate the antithetical gene regulation, ON–OFF–ON. Engineered signal processing filters can be directed to seven orthogonal promoters via adaptive modular DNA binding design. This collection of signal processing filters can be used in collaboration with our established transcriptional programming structure. Kinetic studies show that our collection of signal processing filters can switch between states of gene expression within a few minutes with minimal metabolic burden—representing a paradigm shift in general gene regulation.

scholarly journals Expression and Gene Regulation Network of SOX9 in Skin Metastasis of Gastric Carcinoma Derived From One Special Patient

2021 ◽  
Author(s):  
Guofeng Chen ◽  
Jiyun Zhu ◽  
Tang Yang ◽  
Huifang Wang ◽  
Liegang Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transcription Factors ◽  
Gastric Carcinoma ◽  
Survival Curve ◽  
Clinical Stage ◽  
Mrna Level ◽  
Skin Metastasis ◽  
The Cancer Genome Atlas ◽  
Sox9 Expression

Abstract BackgroundAn exceptional case of a patient with advanced gastric cancer is presented in this study, treated with multiple chemotherapy, radiotherapy and immune regimens, who exhibited regression of one metastatic lesion with concomitant progression of the other lesion during a treatment of PD-1 antibody period. MethodsUsing whole-exome sequencing, TBM, MSI/MSS, PD-1 positive or negative respond measurement, gene function, tumor expression, clinical stage, survival curve, pathopoiesia gene prediction, neoantigen score and immunogenomic approaches. ResultsWe found that SOX9 might mainly participate into the response process of PD-1 antibody in the right skin metastasis. Then, we used sequencing data from the Cancer Genome Atlas database and Gene Expression Omnibus, analyzing SOX9 expression and gene regulation networks in gastric carcinoma (GC). Expression and CNVs were analyzed using Oncomine and Gene Expression Profiling Interactive Analysis tools, at the same time, SOX9 alterations and related pathway were identified using cBioPortal. LinkedOmics and GeneMANIA were used to identify differential mRNA expression with SOX9 and to analyze Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Gene enrichment analysis examined target networks of kinases, miRNAs, transcription factors and PPIs. The results show that SOX9 is overexpressed and the alteration type of SXO9 is mutation in GC. Expression of this gene coding protein is associated with biological interaction networks involving the cell dedifferentiation and WNT signaling process. Functional network analysis indicates that SOX9 mRNA level regulates the RNA process, DNA replication and cell cycle via pathways involving several cancer-related kinases, miRNAs and transcription factors, like casein kinase 2 alpha 1, cyclin dependent kinase 2, Mir296 and Mir214. ConclusionsOur results finally demonstrate that bioinformation analysis efficiently reveals online information of SOX9 expression and potential regulatory networks in GC, laying a foresight for further study of the role of SOX9 and a new PD-1 treatment predictor in gastric carcinogenesis.

scholarly journals RNA interference: what it is and what it does: A potent gene regulator

2004 ◽  
Vol 26 (5) ◽  
pp. 7-10
Author(s):  
Darcey Black ◽  
Sarah Newbury
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Rna Interference ◽  
Metabolic Pathways ◽  
Drug Targets ◽  
Human Cells ◽  
Potential Drug ◽  
Genetic Studies ◽  
Multicellular Organisms ◽  
Potential Drug Targets

RNA interference (RNAi) is a potent and specific way of down-regulating gene expression. It is effective in most multicellular organisms, and every gene in the genome can potentially be targeted, providing that the sequence of the gene is known. It has provided a breakthrough in the study of gene regulation, because the function of a gene can often be deduced by inhibiting its ex-pression. RNAi therefore provides a rapid way of studying the function of known genes in organisms where genetic studies are difficult. Since RNAi is effective in human cells, it is now being used in several ways. These include the elucidation of biochemical and metabolic pathways, validation of potential drug targets, and as a therapeutic in the treatment of disease.

Factors regulating lactoferrin gene expressionThis paper is one of a selection of papers published in this Special Issue, entitled 7th International Conference on Lactoferrin: Structure, Function, and Applications, and has undergone the Journal's usual peer review process.

2006 ◽  
Vol 84 (3) ◽  
pp. 263-267 ◽  
Author(s):  
Christina T. Teng
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transcription Factors ◽  
Nuclear Receptors ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Peer Review Process ◽  
Regulation Of Gene Expression ◽  
Limited Information ◽  
Lactoferrin Gene

Regulation of gene expression by nuclear receptors and transcription factors involves the concerted action of multiple proteins. The process of transcriptional activation involves chromatin modification, nuclear receptor or transcription factor binding to the response element of the promoter, and coregulator recruitment. Despite advances in knowledge pertaining to the molecular mechanisms of gene regulation overall, there is very limited information available on the molecular mechanism of lactoferrin gene regulation. This review will outline novel information relating to general gene regulation and will discuss the current understanding of the regulation of lactoferrin gene expression by nuclear receptors and transcription factors.

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