scholarly journals ASIP promoter variants predict sesame coat color in Shiba Inu dogs

2021 ◽  
Author(s):  
Stepan N. Belyakin ◽  
Daniil A Maksimov ◽  
Maria A Pobedintseva ◽  
Petr P Laktionov ◽  
Dinara R Voronova
Keyword(s):  
Gene Expression ◽  
Coat Color ◽  
Color Pattern ◽  
Gene Promoters ◽  
Incomplete Dominance ◽  
Pigment Synthesis ◽  
New Model ◽  
Different Levels ◽  
Good Agreement

Different patterns of coat color pigmentation in dogs are produced by a sophisticated interaction of several genes. Understanding the mechanisms underlying the diversity of coat colors and their inheritance is important for professional breeders because it helps to predict the phenotypes of the progeny. Although genetics of the main coat colors in dogs is extensively studied, there are types of coat pigmentation that are not explained yet. Recently a new model connected the variants in ASIP gene promoters with different coat colors in dogs. Here we used this model as a framework to investigate the genetics of the rare sesame coat color in Shiba Inu dogs. We determined the combination of two alleles of ASIP gene that determine sesame coat color. This finding can be used by the breeders to produce the dogs with this rare coat color pattern. We also demonstrate the incomplete dominance between the ASIP alleles involved in sesame coat formation. These results are in good agreement with the new model explaining how different levels of ASIP gene expression affect the regulation of pigment synthesis in melanocytes.

scholarly journals Transcriptional enhancers and their communication with gene promoters

2021 ◽  
Author(s):  
Helen Ray-Jones ◽  
Mikhail Spivakov
Keyword(s):  
Gene Expression ◽  
Functional Genomics ◽  
Target Genes ◽  
Gene Control ◽  
Gene Promoters ◽  
Joint Effects ◽  
Transcriptional Enhancers ◽  
Quantitative Understanding ◽  
The Right ◽  
The Way

AbstractTranscriptional enhancers play a key role in the initiation and maintenance of gene expression programmes, particularly in metazoa. How these elements control their target genes in the right place and time is one of the most pertinent questions in functional genomics, with wide implications for most areas of biology. Here, we synthesise classic and recent evidence on the regulatory logic of enhancers, including the principles of enhancer organisation, factors that facilitate and delimit enhancer–promoter communication, and the joint effects of multiple enhancers. We show how modern approaches building on classic insights have begun to unravel the complexity of enhancer–promoter relationships, paving the way towards a quantitative understanding of gene control.

scholarly journals The Stationary Concentrated Vortex Model

Climate ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 39
Author(s):  
Oleg Onishchenko ◽  
Viktor Fedun ◽  
Wendell Horton ◽  
Oleg Pokhotelov ◽  
Natalia Astafieva ◽  
...  
Keyword(s):  
Vortex Structure ◽  
Radial Direction ◽  
Symmetry Axis ◽  
Outer Part ◽  
Vertical Direction ◽  
Axially Symmetric ◽  
New Model ◽  
Vortex Model ◽  
Axis Of Symmetry ◽  
Good Agreement

A new model of an axially-symmetric stationary concentrated vortex for an inviscid incompressible flow is presented as an exact solution of the Euler equations. In this new model, the vortex is exponentially localised, not only in the radial direction, but also in height. This new model of stationary concentrated vortex arises when the radial flow, which concentrates vorticity in a narrow column around the axis of symmetry, is balanced by vortex advection along the symmetry axis. Unlike previous models, vortex velocity, vorticity and pressure are characterised not only by a characteristic vortex radius, but also by a characteristic vortex height. The vortex structure in the radial direction has two distinct regions defined by the internal and external parts: in the inner part the vortex flow is directed upward, and in the outer part it is downward. The vortex structure in the vertical direction can be divided into the bottom and top regions. At the bottom of the vortex the flow is centripetal and at the top it is centrifugal. Furthermore, at the top of the vortex the previously ascending fluid starts to descend. It is shown that this new model of a vortex is in good agreement with the results of field observations of dust vortices in the Earth’s atmosphere.

scholarly journals Hesx1 homeodomain protein represses transcription as a monomer and antagonises transactivation of specific sites as a homodimer

2002 ◽  
Vol 28 (3) ◽  
pp. 193-205 ◽  
Author(s):  
J Quirk ◽  
P Brown
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Binding Site ◽  
Anterior Pituitary ◽  
Homeodomain Protein ◽  
Dependent Manner ◽  
Gene Promoters ◽  
Differentiation Markers ◽  
Proximal Half ◽  
Dna Binding Site

The homeobox repressor Hesx1, expressed throughout Rathke's pouch and required for normal pituitary development, has been implicated in anterior pituitary pathogenesis in man. Prolonged expression of Hesx1 delays the appearance of anterior pituitary terminal differentiation markers in mice, particularly the gonadotroph hormones. We tested if Hesx1 could modulate gonadotrophin gene expression directly, and found that Hesx1 repressed both common alpha subunit (alpha GSU) and luteinising hormone beta-subunit (LH beta) gene promoters. Repression mapped to the Pitx1 homeodomain protein transactivation site in the proximal alpha GSU promoter, but did not map to the equivalent site on LH beta. Hesx1 repression of the alpha GSU Pitx1 site was overridden by co-transfection of Pitx1. In contrast, Hesx1 antagonised Pitx1 transactivation of LH beta in a dose-dependent manner. This was due to monomeric binding of Hesx1 on alpha GSU and homodimerisation on LH beta. The homodimerisation site comprises the Pitx1 DNA binding site and a proximal binding site, and mutation of either inhibited homodimer formation. Conversion of the LH beta Pitx1 DNA binding site to an alpha GSU-type did not promote homodimer formation, arguing that Hesx1 has pronounced site selectivity. Furthermore, mutation of the proximal half of the homodimerisation site blocked Hesx1 antagonisation of Pitx1 transactivation. We conclude that Hesx1 monomers repress gene expression, and homodimers block specific transactivation sites.

Human globin gene promoter sequences are sufficient for specific expression of a hybrid gene transfected into tissue culture cells

1987 ◽  
Vol 7 (1) ◽  
pp. 398-402
Author(s):  
T Rutherford ◽  
A W Nienhuis
Keyword(s):  
Gene Expression ◽  
Globin Gene ◽  
Gene Promoter ◽  
Gene Promoters ◽  
Globin Genes ◽  
Specific Expression ◽  
Tissue Specific ◽  
Promoter Sequences ◽  
Erythroleukemia Cells ◽  
Murine Erythroleukemia

The contribution of the human globin gene promoters to tissue-specific transcription was studied by using globin promoters to transcribe the neo (G418 resistance) gene. After transfection into different cell types, neo gene expression was assayed by scoring colony formation in the presence of G418. In K562 human erythroleukemia cells, which express fetal and embryonic globin genes but not the adult beta-globin gene, the neo gene was expressed strongly from a fetal gamma- or embryonic zeta-globin gene promoter but only weakly from the beta promoter. In murine erythroleukemia cells which express the endogenous mouse beta genes, the neo gene was strongly expressed from both beta and gamma promoters. In two nonerythroid cell lines, human HeLa cells and mouse 3T3 fibroblasts, the globin gene promoters did not allow neo gene expression. Globin-neo genes were integrated in the erythroleukemia cell genomes mostly as a single copy per cell and were transcribed from the appropriate globin gene cap site. We conclude that globin gene promoter sequences extending from -373 to +48 base pairs (bp) (relative to the cap site) for the beta gene, -385 to +34 bp for the gamma gene, and -555 to +38 bp for the zeta gene are sufficient for tissue-specific and perhaps developmentally specific transcription.

Gene-regulatory elements may change the amount, timing, or location of gene expression, cis-Regulation therapy platforms might become a gene therapy to treat many genetic diseases

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Expression ◽  
Genetic Diseases ◽  
Regulatory Elements ◽  
Tissue Type ◽  
Gene Promoters ◽  
Expression Levels ◽  
Cis Regulation ◽  
Gene Regulatory Elements ◽  
Gene Regulatory ◽  
Gene Expression Levels

Changes in gene expression levels above or below a particular threshold may have a dramatic impact on phenotypes, leading to a wide spectrum of human illnesses. Gene-regulatory elements, also known as cis-regulatory elements (CREs), may change the amount, timing, or location (cell/tissue type) of gene expression, whereas mutations in a gene's coding sequence may result in lower or higher gene expression levels resulting in protein loss or gain. Loss-of-function mutations in both genes produce recessive human illness, while haploinsufficient mutations in 65 genes are also known to be deleterious due to function gain, according to the ClinVar1 and ClinGen3 databases. CREs are promoters living near to a gene's transcription start site and switching it on at predefined times, places, and levels. Other distal CREs, like enhancers and silencers, are temporal and tissue-specific control promoters. Enhancers activate promoters, commonly referred to as "promoters," whereas silencers turn them off. Insulators also restrict promiscuous interactions between enhancers and gene promoters. Systematic genomic approaches can help understand the cis-regulatory circuitry of gene expression by highly detecting and functionally defining these CREs. This includes the new use of CRISPR–CRISPR-associated protein 9 (CRISPR–Cas9) and other editing approaches to discover CREs. Cis-Regulation therapy (CRT) provides many promises to heal human ailments. CRT may be used to upregulate or downregulate disease-causing genes due to lower or higher levels of expression, and it may also be used to precisely adjust the expression of genes that assist in alleviating disease features. CRT may employ proteins that generate epigenetic modifications like methylation, histone modification, or gene expression regulation looping. Weighing CRT's advantages and downsides against alternative treatment methods is crucial. CRT platforms might become a practical technique to treat many genetic diseases that now lack treatment alternatives if academics, patient communities, clinicians, regulators and industry work together.

Abstract 40: Disturbed Flow Alters Genomewide DNA Methylation Patterns, Regulating Endothelial Gene Expression and Atherosclerosis

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Jessilyn Dunn ◽  
Haiwei Qiu ◽  
Soyeon Kim ◽  
Daudi Jjingo ◽  
Ryan Hoffman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Western Diet ◽  
Dependent Manner ◽  
Gene Promoters ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Endothelial Gene Expression

Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow (d-flow), which alters gene expression, endothelial function, and atherosclerosis. Here, we show that d-flow regulates genome-wide DNA methylation patterns in a DNA methyltransferase (DNMT)-dependent manner. We found that d-flow induced expression of DNMT1, but not DNMT3a or DNMT3b, in mouse arterial endothelium in vivo and in cultured endothelial cells by oscillatory shear (OS) compared to unidirectional laminar shear in vitro. The DNMT inhibitor 5-Aza-2’deoxycytidine (5Aza) or DNMT1 siRNA significantly reduced OS-induced endothelial inflammation. Moreover, 5Aza reduced lesion formation in two atherosclerosis models using ApoE-/- mice (western diet for 3 months and the partial carotid ligation model with western diet for 3 weeks). To identify the 5Aza mechanisms, we conducted two genome-wide studies: reduced representation bisulfite sequencing (RRBS) and transcript microarray using endothelial-enriched gDNA and RNA, respectively, obtained from the partially-ligated left common carotid artery (LCA exposed to d-flow) and the right contralateral control (RCA exposed to s-flow) of mice treated with 5Aza or vehicle. D-flow induced DNA hypermethylation in 421 gene promoters, which was significantly prevented by 5Aza in 335 genes. Systems biological analyses using the RRBS and the transcriptome data revealed 11 mechanosensitive genes whose promoters were hypermethylated by d-flow but rescued by 5Aza treatment. Of those, five genes contain hypermethylated cAMP-response-elements in their promoters, including the transcription factors HoxA5 and Klf3. Their methylation status could serve as a mechanosensitive master switch in endothelial gene expression. Our results demonstrate that d-flow controls epigenomic DNA methylation patterns in a DNMT-dependent manner, which in turn alters endothelial gene expression and induces atherosclerosis.

scholarly journals Thermal conductivity of unsaturated clay-rocks

2010 ◽  
Vol 14 (1) ◽  
pp. 91-98 ◽  
Author(s):  
D. Jougnot ◽  
A. Revil
Keyword(s):  
Thermal Conductivity ◽  
Porous Material ◽  
Solid Phase ◽  
Model Parameters ◽  
Electrical Parameters ◽  
New Model ◽  
Unsaturated Clay ◽  
Unsaturated Porous Material ◽  
Clay Rocks ◽  
Good Agreement

Abstract. The parameters used to describe the electrical conductivity of a porous material can be used to describe also its thermal conductivity. A new relationship is developed to connect the thermal conductivity of an unsaturated porous material to the thermal conductivity of the different phases of the composite, and two electrical parameters called the first and second Archie's exponents. A good agreement is obtained between the new model and thermal conductivity measurements performed using packs of glass beads and core samples of the Callovo-Oxfordian clay-rocks at different saturations of the water phase. We showed that the three model parameters optimised to fit the new model against experimental data (namely the thermal conductivity of the solid phase and the two Archie's exponents) are consistent with independent estimates. We also observed that the anisotropy of the effective thermal conductivity of the Callovo-Oxfordian clay-rock was mainly due to the anisotropy of the thermal conductivity of the solid phase.

scholarly journals Febrile-range temperature modifies cytokine gene expression in LPS-stimulated macrophages by differentially modifying NF-κB recruitment to cytokine gene promoters

2010 ◽  
Vol 298 (1) ◽  
pp. C171-C181 ◽  
Author(s):  
Zachary A. Cooper ◽  
Arundhati Ghosh ◽  
Aditi Gupta ◽  
Tapan Maity ◽  
Ivor J. Benjamin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Receptor Activation ◽  
Cytokine Gene Expression ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Heat Shock Factor 1 ◽  
Gene Promoters ◽  
Cytokine Gene ◽  
Tnf Α

We previously showed that exposure to febrile-range temperatures (FRT, 39.5–40°C) reduces LPS-induced TNF-α expression, in part through the direct interaction of heat shock factor-1 (HSF1) with the TNF-α gene promoter. However, it is not known whether exposure to FRT also modifies more proximal LPS-induced signaling events. Using HSF1-null mice, we confirmed that HSF1 is required for FRT-induced repression of TNF-α in vitro by LPS-stimulated bone marrow-derived macrophages and in vivo in mice challenged intratracheally with LPS. Exposing LPS-stimulated RAW 264.7 mouse macrophages to FRT reduced TNF-α expression while increasing IL-1β expression despite the two genes sharing a common myeloid differentiation protein-88 (MyD88)-dependent pathway. Global activation of the three LPS-induced signaling intermediates that lead to cytokine gene expression, ERK and p38 MAPKs and NF-κB, was not affected by exposing RAW 264.7 cells to FRT as assessed by ERK and p38 phosphorylation and NF-κB in vitro DNA-binding activity and activation of a NF-κB-dependent synthetic promoter. However, chromatin immunoprecipitation (ChIP) analysis demonstrated that exposure to FRT reduced LPS-induced recruitment of NF-κB p65 to the TNF-α promoter while simultaneously increasing its recruitment to the IL-1β promoter. These data suggest that FRT exerts its effects on cytokine gene expression in a gene-specific manner through distal effects on promoter activation rather than proximal receptor activation and signal transduction.

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