scholarly journals MYC regulates ribosome biogenesis and mitochondrial gene expression programs through interaction with Host Cell Factor-1

2020 ◽  
Author(s):  
Tessa M. Popay ◽  
Jing Wang ◽  
Clare M. Adams ◽  
Simona G. Codreanu ◽  
Stacy Sherrod ◽  
...  
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Ribosome Biogenesis ◽  
Focal Point ◽  
Mitochondrial Gene ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Cancer Therapies ◽  
Host Cell Factor

ABSTRACTThe oncoprotein transcription factor MYC is a major driver of malignancy and a highly-validated but challenging target for development of anti-cancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here, we interrogate how one MYC co-factor, Host Cell Factor (HCF)-1, contributes to MYC activity in a Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets, and demonstrate how modulation of the MYC–HCF-1 interaction influences cell growth, metabolite profiles, global gene expression patterns, and tumor growth in vivo. This work defines HCF-1 as a critical MYC co-factor, places the MYC–HCF-1 interaction in biological context, and highlights HCF-1 as a focal point for development of novel anti-MYC therapies.

scholarly journals MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor–1

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Tessa M Popay ◽  
Jing Wang ◽  
Clare M Adams ◽  
Gregory Caleb Howard ◽  
Simona G Codreanu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Ribosome Biogenesis ◽  
Focal Point ◽  
Mitochondrial Gene ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Host Cell Factor ◽  
Host Cell Factor 1

The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here we interrogate how one MYC co-factor, host cell factor (HCF)–1, contributes to MYC activity in a human Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets and demonstrate how modulation of the MYC–HCF-1 interaction influences cell growth, metabolite profiles, global gene expression patterns, and tumor growth in vivo. This work defines HCF-1 as a critical MYC co-factor, places the MYC–HCF-1 interaction in biological context, and highlights HCF-1 as a focal point for development of novel anti-MYC therapies.

Cryotolerance and global gene-expression patterns of Bos taurus indicus and Bos taurus taurus in vitro- and in vivo-produced blastocysts

2014 ◽  
Vol 26 (8) ◽  
pp. 1129 ◽  
Author(s):  
Mateus J. Sudano ◽  
Ester S. Caixeta ◽  
Daniela M. Paschoal ◽  
Alicio Martins ◽  
Rui Machado ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Bos Taurus ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Embryo Viability ◽  
Bos Taurus Indicus

In a 2 × 2 factorial experimental design, embryo development, cryotolerance and global gene expression of Nellore (Bos taurus indicus) and Simmental (Bos taurus taurus) blastocysts produced in vitro (IVP) and in vivo (multiple ovulation derived embryo, MODE) were assessed. Blastocyst production was higher in Nellore than in Simmental (47.7 ± 2.0% vs 27.0 ± 2.0%) cows. The total numbers of ova or embryos recovered (5.5 ± 0.9 vs 3.7 ± 0.8) and transferable embryos (3.8 ± 1.0 vs 2.3 ± 0.8) per cow were not different between breeds. Simmental and MODE (34.6% and 38.5%, n = 75 and 70) blastocysts had higher survival rates after cryopreservation compared with Nellore and IVP (20.2% and 18.1%, n = 89 and 94) embryos, respectively. Differences between transcriptomes were addressed by principal-component analysis, which indicated that gene expression was affected by subspecies (158 genes), origin (532 genes) and interaction between both subspecies and origin (53 genes). Several functional processes and pathways relevant to lipid metabolism and embryo viability involving differentially expressed genes were identified. The lipid metabolism-related genes were upregulated in Simmental (AUH and ELOVL6) and IVP (ACSL3 and ACSL6) blastocysts. The expression profiles of genes related to mitochondrial metabolism (ATP5B), oxidative stress (GPX4), apoptosis (DAD1, DAP, PRDX2), heat shock (HSPA5), pregnancy (IFNT2, PAG2) and cell differentiation (KRT18) varied between experimental groups.

scholarly journals Identification of gene expression profile in tolerizing murine cardiac allograft by costimulatory blockade

2003 ◽  
Vol 15 (3) ◽  
pp. 199-208 ◽  
Author(s):  
Yuichi Matsui ◽  
Akio Saiura ◽  
Yasuhiko Sugawara ◽  
Masataka Sata ◽  
Katsutoshi Naruse ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Tolerance Induction ◽  
Global Gene Expression ◽  
Interferon Γ ◽  
Immunologic Tolerance ◽  
Inflammatory Factors ◽  
Cytokines And Chemokines ◽  
Cardiac Allografts

The induction of specific tolerance would be the ultimate achievement in transplant immunology, but the precise mechanisms of immunologic tolerance remain largely unknown. Here, we investigated global gene expression analysis in tolerizing murine cardiac allografts by means of oligonucleotide microarrays. Tolerance induction was achieved in cardiac allografts from BALB/c to C57BL/6 mice by daily intraperitoneal injection of anti-CD80 and anti-CD86 monoclonal antibodies (mAbs). Comparative analysis revealed 64 genes to be induced more extensively in the tolerizing than in the syngeneic isografts, and 16 genes than in the rejecting allografts. Two genes were specifically upregulated in the tolerizing allografts. In the tolerizing allografts there were induced marked expressions of a number of genes for pro-inflammatory factors, including interferon-γ-inducible cytokines and chemokines, as well as apoptosis-related genes, which were also upregulated in the rejecting allografts. Moreover, these gene expression patterns continued to be upregulated more than 70 days posttransplant. These results provide evidence that immunologic tolerance can be induced and maintained in the presence of prominent pro-inflammatory gene expression in vivo.

scholarly journals Mitochondrial Mistranslation in Brain Provokes a Metabolic Response Which Mitigates the Age-Associated Decline in Mitochondrial Gene Expression

2021 ◽  
Vol 22 (5) ◽  
pp. 2746
Author(s):  
Dimitri Shcherbakov ◽  
Reda Juskeviciene ◽  
Adrián Cortés Sanchón ◽  
Margarita Brilkova ◽  
Hubert Rehrauer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Response ◽  
Mitochondrial Gene ◽  
Tca Cycle ◽  
Brain Mitochondria ◽  
Mitochondrial Gene Expression ◽  
Rna Seq ◽  
The Tca Cycle ◽  
Neurological Phenotype

Mitochondrial misreading, conferred by mutation V338Y in mitoribosomal protein Mrps5, in-vivo is associated with a subtle neurological phenotype. Brain mitochondria of homozygous knock-in mutant Mrps5V338Y/V338Y mice show decreased oxygen consumption and reduced ATP levels. Using a combination of unbiased RNA-Seq with untargeted metabolomics, we here demonstrate a concerted response, which alleviates the impaired functionality of OXPHOS complexes in Mrps5 mutant mice. This concerted response mitigates the age-associated decline in mitochondrial gene expression and compensates for impaired respiration by transcriptional upregulation of OXPHOS components together with anaplerotic replenishment of the TCA cycle (pyruvate, 2-ketoglutarate).

scholarly journals Compendium of Methods to Uncover RNA-Protein Interactions In Vivo

2021 ◽  
Vol 4 (1) ◽  
pp. 22
Author(s):  
Mrinmoyee Majumder ◽  
Viswanathan Palanisamy
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Expression Patterns ◽  
Control Of Gene Expression ◽  
Regulatory Pathways ◽  
Advantages And Disadvantages ◽  
Protein Nucleic Acid

Control of gene expression is critical in shaping the pro-and eukaryotic organisms’ genotype and phenotype. The gene expression regulatory pathways solely rely on protein–protein and protein–nucleic acid interactions, which determine the fate of the nucleic acids. RNA–protein interactions play a significant role in co- and post-transcriptional regulation to control gene expression. RNA-binding proteins (RBPs) are a diverse group of macromolecules that bind to RNA and play an essential role in RNA biology by regulating pre-mRNA processing, maturation, nuclear transport, stability, and translation. Hence, the studies aimed at investigating RNA–protein interactions are essential to advance our knowledge in gene expression patterns associated with health and disease. Here we discuss the long-established and current technologies that are widely used to study RNA–protein interactions in vivo. We also present the advantages and disadvantages of each method discussed in the review.

A Global Vista of the Epigenomic State of the Mouse Submandibular Gland

2021 ◽  
pp. 002203452110120
Author(s):  
C. Gluck ◽  
S. Min ◽  
A. Oyelakin ◽  
M. Che ◽  
E. Horeth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Control ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Submandibular Salivary Gland ◽  
Data Sets ◽  
Control Mechanisms ◽  
Chromatin Immunoprecipitation Sequencing

The parotid, submandibular, and sublingual glands represent a trio of oral secretory glands whose primary function is to produce saliva, facilitate digestion of food, provide protection against microbes, and maintain oral health. While recent studies have begun to shed light on the global gene expression patterns and profiles of salivary glands, particularly those of mice, relatively little is known about the location and identity of transcriptional control elements. Here we have established the epigenomic landscape of the mouse submandibular salivary gland (SMG) by performing chromatin immunoprecipitation sequencing experiments for 4 key histone marks. Our analysis of the comprehensive SMG data sets and comparisons with those from other adult organs have identified critical enhancers and super-enhancers of the mouse SMG. By further integrating these findings with complementary RNA-sequencing based gene expression data, we have unearthed a number of molecular regulators such as members of the Fox family of transcription factors that are enriched and likely to be functionally relevant for SMG biology. Overall, our studies provide a powerful atlas of cis-regulatory elements that can be leveraged for better understanding the transcriptional control mechanisms of the mouse SMG, discovery of novel genetic switches, and modulating tissue-specific gene expression in a targeted fashion.

scholarly journals Altered Proteolysis and Global Gene Expression in Hepatitis B Virus X Transgenic Mouse Liver

2006 ◽  
Vol 80 (3) ◽  
pp. 1405-1413 ◽  
Author(s):  
Zongyi Hu ◽  
Zhensheng Zhang ◽  
Jin Woo Kim ◽  
Ying Huang ◽  
T. Jake Liang
Keyword(s):  
Gene Expression ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mouse ◽  
Mouse Liver ◽  
Global Gene Expression ◽  
Pleiotropic Effect ◽  
B Virus ◽  
Number Of Genes

ABSTRACT Hepatitis B virus X (HBX) is essential for the productive infection of hepatitis B virus (HBV) in vivo and has a pleiotropic effect on host cells. We have previously demonstrated that the proteasome complex is a cellular target of HBX, that HBX alters the proteolytic activity of proteasome in vitro, and that inhibition of proteasome leads to enhanced viral replication, suggesting that HBX and proteasome interaction plays a crucial role in the life cycle and pathogenesis of HBV. In the present study, we tested the effect of HBX on the proteasome activities in vivo in a transgenic mouse model in which HBX expression is developmentally regulated by the mouse major urinary promoter in the liver. In addition, microarray analysis was performed to examine the effect of HBX expression on the global gene expression profile of the liver. The results showed that the peptidase activities of the proteasome were reduced in the HBX transgenic mouse liver, whereas the activity of another cellular protease was elevated, suggesting a compensatory mechanism in protein degradation. In the microarray analysis, diverse genes were altered in the HBX mouse livers and the number of genes with significant changes increased progressively with age. Functional clustering showed that a number of genes involved in transcription and cell growth were significantly affected in the HBX mice, possibly accounting for the observed pleiotropic effect of HBX. In particular, insulin-like growth factor-binding protein 1 was down-regulated in the HBX mouse liver. The down-regulation was similarly observed during acute woodchuck hepatitis virus infection. Other changes including up-regulation of proteolysis-related genes may also contribute to the profound alterations of liver functions in HBV infection.

scholarly journals WILD-seq: Clonal deconvolution of transcriptomic signatures of sensitivity and resistance to cancer therapeutics in vivo.

2021 ◽  
Author(s):  
Sophia Alisa Wild ◽  
Ian Gordon Cannell ◽  
Katarzyna Kania ◽  
Gregory James Hannon ◽  
Kirsty Sawicka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Therapeutics ◽  
Cancer Therapies ◽  
Major Barrier ◽  
Major Mechanism ◽  
Stress Protection ◽  
Taxane Resistance ◽  
Taxane Chemotherapy ◽  
Clonal Abundance

Tumour heterogeneity is thought to be a major barrier to successful cancer treatment due to the presence of drug resistant clonal lineages. However, identifying the characteristics of such lineages that underpin resistance to therapy has remained challenging. Here we present WILD-seq; Wholistic Interrogation of Lineage Dynamics by sequencing, a platform that leverages expressed barcodes to simultaneously map clonal identities and transcriptional states at single cell resolution. Our optimised pipeline ensures recurrent representation of clonal lineages across animals and samples, facilitating analysis of clonal dynamics under perturbation. Application of WILD-seq to two triple negative mammary carcinoma mouse models, identified changes in clonal abundance, gene expression and microenvironment in response to JQ1 or taxane chemotherapy. WILD-seq reveals oxidative stress protection as a major mechanism of taxane resistance that renders our tumour models collaterally sensitive to non-essential amino acid deprivation. In summary, WILD-seq enables facile coupling of lineage and gene expression in vivo to elucidate clone-specific pathways of resistance to cancer therapies.

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