scholarly journals In vivo FirreandDxz4deletion elucidates roles for autosomal gene regulation

2019 ◽  
Author(s):  
Daniel Andergassen ◽  
Zachary D. Smith ◽  
Jordan P. Lewandowski ◽  
Chiara Gerhardinger ◽  
Alexander Meissner ◽  
...  
Keyword(s):  
Gene Regulation ◽  
X Chromosome ◽  
Autosomal Gene ◽  
Double Deletion ◽  
Gene Sets ◽  
Specific Manner ◽  
Main Driver ◽  
Organ Specific ◽  
Transcriptional Effect

AbstractRecent evidence has determined that the conserved X chromosome “mega-structures” controlled by theFirreandDxz4alleles are not required for X chromosome inactivation (XCI) in cell lines. Here we determined thein vivocontribution of these alleles by generating mice carrying a single or double deletion ofFirreandDxz4. We found that these mutants are viable, fertile and show no defect in random or imprinted XCI. However, the lack of these elements results in many dysregulated genes on autosomes in an organ-specific manner. By comparing the dysregulated genes between the single and double deletion, we identified superloop, megadomain, andFirrelocus dependent gene sets. The largest transcriptional effect was observed in all strains lacking theFirrelocus, indicating that this locus is the main driver for these autosomal expression signatures. Collectively, these findings suggest that these X-linked loci are involved in autosomal gene regulation rather than XCI biology.

scholarly journals In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Daniel Andergassen ◽  
Zachary D Smith ◽  
Jordan P Lewandowski ◽  
Chiara Gerhardinger ◽  
Alexander Meissner ◽  
...  
Keyword(s):  
Gene Regulation ◽  
X Chromosome ◽  
Autosomal Gene ◽  
Double Deletion ◽  
Gene Sets ◽  
Specific Manner ◽  
Main Driver ◽  
Organ Specific ◽  
Transcriptional Effect

Recent evidence has determined that the conserved X chromosome mega-structures controlled by the Firre and Dxz4 loci are not required for X chromosome inactivation (XCI) in cell lines. Here, we examined the in vivo contribution of these loci by generating mice carrying a single or double deletion of Firre and Dxz4. We found that these mutants are viable, fertile and show no defect in random or imprinted XCI. However, the lack of these elements results in many dysregulated genes on autosomes in an organ-specific manner. By comparing the dysregulated genes between the single and double deletion, we identified superloop, megadomain, and Firre locus-dependent gene sets. The largest transcriptional effect was observed in all strains lacking the Firre locus, indicating that this locus is the main driver for these autosomal expression signatures. Collectively, these findings suggest that these X-linked loci are involved in autosomal gene regulation rather than XCI biology.

scholarly journals Author response: In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation

2019 ◽  
Author(s):  
Daniel Andergassen ◽  
Zachary D Smith ◽  
Jordan P Lewandowski ◽  
Chiara Gerhardinger ◽  
Alexander Meissner ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Author Response ◽  
Autosomal Gene

scholarly journals Translation elongation rate varies among organs and decreases with age

2020 ◽  
Author(s):  
Maxim V Gerashchenko ◽  
Zalan Peterfi ◽  
Sun Hee Yim ◽  
Vadim N Gladyshev
Keyword(s):  
Translation Initiation ◽  
Elongation Rate ◽  
Ribosome Profiling ◽  
Translation Elongation ◽  
Time Resolved ◽  
Specific Manner ◽  
Organ Specific ◽  
Cell Type Specific ◽  
Polypeptide Chains

Abstract There has been a surge of interest towards targeting protein synthesis to treat diseases and extend lifespan. Despite the progress, few options are available to assess translation in live animals, as their complexity limits the repertoire of experimental tools to monitor and manipulate processes within organs and individual cells. It this study, we developed a labeling-free method for measuring organ- and cell-type-specific translation elongation rates in vivo. It is based on time-resolved delivery of translation initiation and elongation inhibitors in live animals followed by ribosome profiling. It also reports translation initiation sites in an organ-specific manner. Using this method, we found that the elongation rates differ more than 50% among mouse organs and determined them to be 6.8, 5.0 and 4.3 amino acids per second for liver, kidney, and skeletal muscle, respectively. We further found that the elongation rate is reduced by 20% between young adulthood and mid-life. Thus, translation, a major metabolic process in cells, is tightly regulated at the level of elongation of nascent polypeptide chains.

Orphan Nuclear Receptors and the Regulation of Nutrient Metabolism: Understanding Obesity

Physiology ◽  
2012 ◽  
Vol 27 (3) ◽  
pp. 156-166 ◽  
Author(s):  
Michael A. Pearen ◽  
George E. O. Muscat
Keyword(s):  
Nuclear Receptors ◽  
Energy Homeostasis ◽  
Hormone Receptors ◽  
Orphan Nuclear Receptors ◽  
Nutrient Metabolism ◽  
Genetic Studies ◽  
Specific Manner ◽  
Organ Specific

Nuclear hormone receptors (NRs) are a superfamily of eukaryotic ligand-dependent transcription factors that translate endocrine, metabolic, nutritional, developmental, and pathophysiological signals into gene regulation. Members of the NR superfamily (on the basis of sequence homology) that lack identified natural and/or synthetic ligands are/were classified as “orphan” NRs. These members of the NR superfamily are abundantly expressed in tissues associated with major metabolic activity, such as skeletal muscle, adipose, and liver. Subsequently, in vivo genetic studies on these orphan NRs and exploitation of novel natural and synthetic agonists has revealed that orphan NRs regulate 1) carbohydrate, lipid, and energy homeostasis in a tissue-specific manner, and 2) the pathophysiology of dyslipidemia, obesity, Type 2 diabetes, and cardiovascular disease. This review discusses key studies that have implicated the orphan NRs as organ-specific regulators of metabolism and mediators of adverse pathophysiological effects. The emerging discovery of novel endogenous orphan NR ligands and synthetic agonists has provided the foundation for therapeutic exploitation of the orphans in the treatment of metabolic disease.

In Vivo Intermittent Hypoxia Induces NFκB Activity In An Organ-specific Manner

2010 ◽  
Author(s):  
John F. Garvey ◽  
Susan Fitzpatrick ◽  
Murtaza Tambuwala ◽  
Deirdre Edge ◽  
Aisling O'Connor ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Specific Manner ◽  
Organ Specific

A Physiologic Regulator of Collagen-Induced Platelet Aggregation: Inhibition by Clq

1981 ◽  
Vol 45 (02) ◽  
pp. 110-115 ◽  
Author(s):  
György Csákó ◽  
Eva A Suba
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Platelet Reactivity ◽  
High Specificity ◽  
Turbidimetric Method ◽  
Specific Manner ◽  
Aggregation Inhibition ◽  
Different Tissues

SummaryPlatelet aggregations were studied by a turbidimetric method in citrated human platelet-rich plasmas (PRP) in vitro. Human Clq inhibited the aggregations caused by collagens derived from different tissues and species. Clq was needed by weight in comparable quantities to collagen for neutralizing the aggregating effect. The dependence of the inhibitory reaction on the preincubation of platelets with Clq and the differences in the occurrence of aggregating substances in supernatants of PRP triggered with collagen in the presence or absence of Clq, confirmed that Clq exerts its effect by preventing fixation of collagen to platelets. In addition, the high specificity of the inhibitory action of Clq for collagen-induced platelet aggregation was demonstrated by results obtained for testing a variety of aggregating agents in combination with Clq and/or collagen.Since normal concentrations of Clq in the blood are in the range of inhibitory doses of Clq for collagen-induced platelet aggregations in vitro and upon activation of complement Clq is known to dissociate from Cl, it is proposed that Clq may participate in a highly specific manner in regulating platelet reactivity to collagen in vivo.

scholarly journals Clues of in vivo nuclear gene regulation by mitochondrial short non-coding RNAs

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marco Passamonti ◽  
Marco Calderone ◽  
Manuel Delpero ◽  
Federico Plazzi
Keyword(s):  
Gene Regulation ◽  
Nuclear Gene ◽  
Non Coding Rnas ◽  
Nuclear Gene Regulation

scholarly journals Mathematical model for the thermal enhancement of radiation response: thermodynamic approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adriana M. De Mendoza ◽  
Soňa Michlíková ◽  
Johann Berger ◽  
Jens Karschau ◽  
Leoni A. Kunz-Schughart ◽  
...  
Keyword(s):  
Protein Denaturation ◽  
Collateral Damage ◽  
Hyperthermia Treatment ◽  
Reversible Process ◽  
Technological Advances ◽  
Thermal Enhancement ◽  
Main Driver ◽  
Definition Of

AbstractRadiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Recent technological advances in the clinical application has revitalized hyperthermia treatment (HT) as an option to improve radiotherapy (RT) outcomes. Understanding the synergistic effect of simultaneous thermoradiotherapy via mathematical modelling is essential for treatment planning. We here propose a theoretical model in which the thermal enhancement ratio (TER) relates to the cell fraction being radiosensitised by the infliction of sublethal damage through HT. Further damage finally kills the cell or abrogates its proliferative capacity in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our findings point towards an improved definition of thermal dose in concordance with the thermodynamics of protein denaturation. Our predictions well reproduce experimental in vitro and in vivo data, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.

A GATA3 Targeting Nucleic Acid Nanocapsule for In Vivo Gene Regulation in Asthma

ACS Nano ◽  
2021 ◽  
Author(s):  
Tyler D. Gavitt ◽  
Alyssa K. Hartmann ◽  
Shraddha S. Sawant ◽  
Arlind B. Mara ◽  
Steven M. Szczepanek ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Nucleic Acid
Sign in / Sign up

Export Citation Format

Share Document