scholarly journals 3. Safety Assessment of SIN LVs Harboring Chromatin Insulators in the Sensitive Cdkn2a-/- In Vivo Genotoxicity Assay Show Enhancer-Blocking Activity of Specific Insulator Sequences

2015 ◽  
Vol 23 ◽  
pp. S2
Author(s):  
Monica Volpin ◽  
Andrea Calabria ◽  
Daniela Cesana ◽  
Erika Tenderini ◽  
Fabrizio Benedicenti ◽  
...  
Keyword(s):  
Safety Assessment ◽  
Blocking Activity ◽  
Enhancer Blocking

scholarly journals A nuclear matrix attachment site in the 4q35 locus has an enhancer-blocking activity in vivo: Implications for the facio-scapulo-humeral dystrophy

2007 ◽  
Vol 18 (1) ◽  
pp. 39-45 ◽  
Author(s):  
A. Petrov ◽  
J. Allinne ◽  
I. Pirozhkova ◽  
D. Laoudj ◽  
M. Lipinski ◽  
...  
Keyword(s):  
Nuclear Matrix ◽  
Attachment Site ◽  
Blocking Activity ◽  
Enhancer Blocking

scholarly journals Rasgrf1 Imprinting Is Regulated by a CTCF-Dependent Methylation-Sensitive Enhancer Blocker

2005 ◽  
Vol 25 (24) ◽  
pp. 11184-11190 ◽  
Author(s):  
Bongjune Yoon ◽  
Herry Herman ◽  
Benjamin Hu ◽  
Yoon Jung Park ◽  
Anders Lindroth ◽  
...  
Keyword(s):  
Binding Sites ◽  
Repeated Sequence ◽  
Ctcf Binding ◽  
Paternal Allele ◽  
Maternal Allele ◽  
Binary Switch ◽  
Blocking Activity ◽  
Enhancer Blocking

ABSTRACT Imprinted methylation of the paternal Rasgrf1 allele in mice occurs at a differentially methylated domain (DMD) 30 kbp 5′ of the promoter. A repeated sequence 3′ of the DMD regulates imprinted methylation, which is required for imprinted expression. Here we identify the mechanism by which methylation controls imprinting. The DMD is an enhancer blocker that binds CTCF in a methylation-sensitive manner. CTCF bound to the unmethylated maternal allele silences expression. CTCF binding to the paternal allele is prevented by repeat-mediated methylation, allowing expression. Optimal in vitro enhancer-blocking activity requires CTCF binding sites. The enhancer blocker can be bypassed in vivo and imprinting abolished by placing an extra enhancer proximal to the promoter. Together, the repeats and the DMD constitute a binary switch that regulates Rasgrf1 imprinting.

Ultrasound-based Safety Assessment during Moving Organ Tracking Towards In Vivo Focused Ultrasound Therapy

2019 ◽  
Author(s):  
A Mariani ◽  
◽  
L Morchi ◽  
A Diodato ◽  
A Cafarelli ◽  
...  
Keyword(s):  
Safety Assessment ◽  
Focused Ultrasound ◽  
Ultrasound Therapy

In-vivo anti-inflammatory activity and safety assessment of the aqueous extract of Algerian Erica arborea L. (Ericaceae) aerial parts

2021 ◽  
Vol 271 ◽  
pp. 113881
Author(s):  
Djouher Amroun ◽  
Meriem Hamoudi ◽  
Seddik Khennouf ◽  
Sabrina Boutefnouchet ◽  
Daoud Harzallah ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Safety Assessment ◽  
Inflammatory Activity ◽  
Aerial Parts ◽  
Erica Arborea ◽  
Anti Inflammatory

scholarly journals Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ivy Aneas ◽  
Donna C. Decker ◽  
Chanie L. Howard ◽  
Débora R. Sobreira ◽  
Noboru J. Sakabe ◽  
...  
Keyword(s):  
Association Studies ◽  
Regulatory Region ◽  
Airway Epithelial Cells ◽  
Genome Wide Association Studies ◽  
Airway Epithelial ◽  
Allele Specific ◽  
Enhancer Blocking ◽  
Underlying Mechanisms

AbstractGenome-wide association studies (GWAS) have implicated the IL33 locus in asthma, but the underlying mechanisms remain unclear. Here, we identify a 5 kb region within the GWAS-defined segment that acts as an enhancer-blocking element in vivo and in vitro. Chromatin conformation capture showed that this 5 kb region loops to the IL33 promoter, potentially regulating its expression. We show that the asthma-associated single nucleotide polymorphism (SNP) rs1888909, located within the 5 kb region, is associated with IL33 gene expression in human airway epithelial cells and IL-33 protein expression in human plasma, potentially through differential binding of OCT-1 (POU2F1) to the asthma-risk allele. Our data demonstrate that asthma-associated variants at the IL33 locus mediate allele-specific regulatory activity and IL33 expression, providing a mechanism through which a regulatory SNP contributes to genetic risk of asthma.

scholarly journals Multiple interactions are involved in a highly specific association of the Mod(mdg4)-67.2 isoform with the Su(Hw) sites in Drosophila

Open Biology ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. 170150 ◽  
Author(s):  
Larisa Melnikova ◽  
Margarita Kostyuchenko ◽  
Varvara Molodina ◽  
Alexander Parshikov ◽  
Pavel Georgiev ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Specific Interaction ◽  
Btb Domain ◽  
Rich Domain ◽  
Blocking Activity ◽  
Transgenic Lines ◽  
Enhancer Blocking ◽  
Specific Association ◽  
Protein Variants ◽  
Multiple Interactions

The best-studied Drosophila insulator complex consists of two BTB-containing proteins, the Mod(mdg4)-67.2 isoform and CP190, which are recruited to the chromatin through interactions with the DNA-binding Su(Hw) protein. It was shown previously that Mod(mdg4)-67.2 is critical for the enhancer-blocking activity of the Su(Hw) insulators and it differs from more than 30 other Mod(mdg4) isoforms by the C-terminal domain required for a specific interaction with Su(Hw) only. The mechanism of the highly specific association between Mod(mdg4)-67.2 and Su(Hw) is not well understood. Therefore, we have performed a detailed analysis of domains involved in the interaction of Mod(mdg4)-67.2 with Su(Hw) and CP190. We found that the N-terminal region of Su(Hw) interacts with the glutamine-rich domain common to all the Mod(mdg4) isoforms. The unique C-terminal part of Mod(mdg4)-67.2 contains the Su(Hw)-interacting domain and the FLYWCH domain that facilitates a specific association between Mod(mdg4)-67.2 and the CP190/Su(Hw) complex. Finally, interaction between the BTB domain of Mod(mdg4)-67.2 and the M domain of CP190 has been demonstrated. By using transgenic lines expressing different protein variants, we have shown that all the newly identified interactions are to a greater or lesser extent redundant, which increases the reliability in the formation of the protein complexes.

scholarly journals Safety Assessment and Biological Effects of a New Cold Processed SilEmulsion for Dermatological Purpose

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Sara Raposo ◽  
Ana Salgado ◽  
Lídia Gonçalves ◽  
Pedro C. Pinto ◽  
Manuela Urbano ◽  
...  
Keyword(s):  
Safety Assessment ◽  
Biological Effects ◽  
Response Assessment ◽  
Skin Surface ◽  
Patch Tests ◽  
Hazard Exposure ◽  
Margin Of Safety ◽  
Skin Surface Lipids

It is of crucial importance to evaluate the safety profile of the ingredients used in dermatological emulsions. A suitable equilibrium between safety and efficacy is a pivotal concern before the marketing of a dermatological product. The aim was to assess the safety and biological effects of a new cold processed silicone-based emulsion (SilEmulsion). The hazard, exposure, and dose-response assessment were used to characterize the risk for each ingredient. EpiSkin assay and human repeat insult patch tests were performed to compare the theoretical safety assessment toin vitroandin vivodata. The efficacy of the SilEmulsion was studied using biophysical measurements in human volunteers during 21 days. According to the safety assessment of the ingredients, 1,5-pentanediol was an ingredient of special concern since its margin of safety was below the threshold of 100 (36.53). EpiSkin assay showed that the tissue viability after the application of the SilEmulsion was 92 ± 6% and, thus considered nonirritant to the skin. The human studies confirmed that the SilEmulsion was not a skin irritant and did not induce any sensitization on the volunteers, being safe for human use. Moreover, biological effects demonstrated that the SilEmulsion increased both the skin hydration and skin surface lipids.

Sign in / Sign up

Export Citation Format

Share Document