scholarly journals Lysine demethylase 7a regulates murine anterior-posterior development by modulating the transcription of Hox gene cluster

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Yoshiki Higashijima ◽  
Nao Nagai ◽  
Masamichi Yamamoto ◽  
Taro Kitazawa ◽  
Yumiko K. Kawamura ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Axial Skeleton ◽  
Regulatory Mechanisms ◽  
Vertebrate Development ◽  
Post Translational Modifications ◽  
Body Patterning ◽  
Temporal And Spatial ◽  
Lysine Demethylase ◽  
Anterior Posterior

AbstractTemporal and spatial colinear expression of the Hox genes determines the specification of positional identities during vertebrate development. Post-translational modifications of histones contribute to transcriptional regulation. Lysine demethylase 7A (Kdm7a) demethylates lysine 9 or 27 di-methylation of histone H3 (H3K9me2, H3K27me2) and participates in the transcriptional activation of developmental genes. However, the role of Kdm7a during mouse embryonic development remains to be elucidated. Herein, we show that Kdm7a−/− mouse exhibits an anterior homeotic transformation of the axial skeleton, including an increased number of presacral elements. Importantly, posterior Hox genes (caudally from Hox9) are specifically downregulated in the Kdm7a−/− embryo, which correlates with increased levels of H3K9me2, not H3K27me2. These observations suggest that Kdm7a controls the transcription of posterior Hox genes, likely via its demethylating activity, and thereby regulating the murine anterior-posterior development. Such epigenetic regulatory mechanisms may be harnessed for proper control of coordinate body patterning in vertebrates.

scholarly journals Lysine demethylase 7a regulates the anterior-posterior development in mouse by modulating the transcription of Hox gene cluster

2019 ◽  
Author(s):  
Yoshiki Higashijima ◽  
Nao Nagai ◽  
Taro Kitazawa ◽  
Yumiko Kawamura ◽  
Akashi Taguchi ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Axial Skeleton ◽  
Regulatory Mechanisms ◽  
Vertebrate Development ◽  
Post Translational Modifications ◽  
Body Patterning ◽  
Temporal And Spatial ◽  
Lysine Demethylase ◽  
Anterior Posterior

SUMMARYTemporal and spatial colinear expression of the Hox genes determines the specification of positional identities during vertebrate development. Post-translational modifications of histones contribute to transcriptional regulation. Lysine demethylase 7A (Kdm7a) demethylates lysine 9 di-methylation of histone H3 (H3K9me2) and participates in the transcriptional activation of developmental genes. However, the role of Kdm7a during mouse embryonic development remains to be elucidated. Here, we show that Kdm7a−/− mouse exhibits an anterior homeotic transformation of the axial skeleton, including an increased number of presacral elements. Importantly, posterior Hox genes (caudally from Hox9) are specifically downregulated in the Kdm7a−/− embryo, which correlates with increased levels of H3K9me2. These observations suggest that Kdm7a controls the transcription of posterior Hox genes, likely via its demethylating activity, and thereby regulating the murine anterior-posterior development. Such epigenetic regulatory mechanisms may be harnessed for the proper control of coordinate body patterning in vertebrates.

scholarly journals A genetic analysis reveals novel histone residues required for transcriptional reprogramming upon stress

2020 ◽  
Vol 48 (7) ◽  
pp. 3455-3475
Author(s):  
Cristina Viéitez ◽  
Gerard Martínez-Cebrián ◽  
Carme Solé ◽  
René Böttcher ◽  
Clement M Potel ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Growth Conditions ◽  
Proof Of Concept ◽  
Transcriptional Program ◽  
Post Translational Modifications ◽  
Transcriptional Reprogramming ◽  
Histone Ptms ◽  
Response To Stress ◽  
State Growth

Abstract Cells have the ability to sense, respond and adapt to environmental fluctuations. Stress causes a massive reorganization of the transcriptional program. Many examples of histone post-translational modifications (PTMs) have been associated with transcriptional activation or repression under steady-state growth conditions. Comparatively less is known about the role of histone PTMs in the cellular adaptive response to stress. Here, we performed high-throughput genetic screenings that provide a novel global map of the histone residues required for transcriptional reprogramming in response to heat and osmotic stress. Of note, we observed that the histone residues needed depend on the type of gene and/or stress, thereby suggesting a ‘personalized’, rather than general, subset of histone requirements for each chromatin context. In addition, we identified a number of new residues that unexpectedly serve to regulate transcription. As a proof of concept, we characterized the function of the histone residues H4-S47 and H4-T30 in response to osmotic and heat stress, respectively. Our results uncover novel roles for the kinases Cla4 and Ste20, yeast homologs of the mammalian PAK2 family, and the Ste11 MAPK as regulators of H4-S47 and H4-T30, respectively. This study provides new insights into the role of histone residues in transcriptional regulation under stress conditions.

scholarly journals Axial skeleton anterior-posterior patterning is regulated through feedback regulation between Meis transcription factors and retinoic acid

2020 ◽  
Author(s):  
Alejandra C. López-Delgado ◽  
Irene Delgado ◽  
Vanessa Cadenas ◽  
Fátima Sánchez-Cabo ◽  
Miguel Torres
Keyword(s):  
Transcription Factors ◽  
Retinoic Acid ◽  
Feedback Regulation ◽  
Axial Skeleton ◽  
Hox Proteins ◽  
Axial Patterning ◽  
Skeletal Defects ◽  
Hox Protein ◽  
Anterior Posterior

ABSTRACTVertebrate axial skeletal patterning is controlled by coordinated collinear expression of Hox genes and axial level-dependent activity of Hox protein combinations. Transcription factors of the Meis family act as cofactors of Hox proteins and profusely bind to Hox complex DNA, however their roles in mammalian axial patterning have not been established. Similarly, retinoic acid (RA) is known to regulate axial skeletal element identity through the transcriptional activity of its receptors, however, whether this role is related to Meis/Hox activity in axial patterning remains unknown. Here we study the role of Meis in axial skeleton formation and its relationship to the RA pathway by characterizing Meis1, Meis2 and Raldh2 mutant mice. Meis elimination produces axial skeleton defects without affecting Hox gene transcription, including vertebral homeotic transformations and rib mis-patterning associated to defects in the hypaxial myotome. While Raldh2 and Meis positively regulate each other, Raldh2 elimination largely recapitulates the defects associated to Meis-deficiency and Meis overexpression rescues the axial skeletal defects in Raldh2 mutants. We propose a Meis-RA positive feedback loop whose output is Meis levels and is essential to establish anterior-posterior identities and pattern of the vertebrate axial skeleton.

Role of molecular chaperones in steroid receptor action

2004 ◽  
Vol 40 ◽  
pp. 41-58 ◽  
Author(s):  
William B Pratt ◽  
Mario D Galigniana ◽  
Yoshihiro Morishima ◽  
Patrick J M Murphy
Keyword(s):  
Transcriptional Activation ◽  
Protein Trafficking ◽  
Steroid Receptors ◽  
Transcriptional Regulatory ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Receptor Action ◽  
Binding Cleft ◽  
Hsp 90

Unliganded steroid receptors are assembled into heterocomplexes with heat-shock protein (hsp) 90 by a multiprotein chaperone machinery. In addition to binding the receptors at the chaperone site, hsp90 binds cofactors at other sites that are part of the assembly machinery, as well as immunophilins that connect the assembled receptor-hsp90 heterocomplexes to a protein trafficking pathway. The hsp90-/hsp70-based chaperone machinery interacts with the unliganded glucocorticoid receptor to open the steroid-binding cleft to access by a steroid, and the machinery interacts in very dynamic fashion with the liganded, transformed receptor to facilitate its translocation along microtubular highways to the nucleus. In the nucleus, the chaperone machinery interacts with the receptor in transcriptional regulatory complexes after hormone dissociation to release the receptor and terminate transcriptional activation. By forming heterocomplexes with hsp90, the chaperone machinery stabilizes the receptor to degradation by the ubiquitin-proteasome pathway of proteolysis.

Giscience in the Mountain Geography

2010 ◽  
Vol 27 (1-2) ◽  
pp. 81-90
Author(s):  
Krishna Poudel
Keyword(s):  
Spatial Data ◽  
Environmental Data ◽  
Temporal Data ◽  
Observation Systems ◽  
Research Findings ◽  
Temporal And Spatial ◽  
Temporal And Spatial Characteristics ◽  
Mountain Geography ◽  
Different Sources

Mountains have distinct geography and are dynamic in nature compared to the plains. 'Verticality' and 'variation' are two fundamental specificities of the mountain geography. They possess distinct temporal and spatial characteristics in a unique socio-cultural setting. There is an ever increasing need for spatial and temporal data for planning and management activities; and Geo Information (GI) Science (including Geographic Information and Earth Observation Systems). This is being recognized more and more as a common platform for integrating spatial data with social, economic and environmental data and information from different sources. This paper investigates the applicability and challenges of GISscience in the context of mountain geography with ample evidences and observations from the mountain specific publications, empirical research findings and reports. The contextual explanation of mountain geography, mountain specific problems, scientific concerns about the mountain geography, advances in GIScience, the role of GIScience for sustainable development, challenges on application of GIScience in the contexts of mountains are the points of discussion. Finally, conclusion has been made with some specific action oriented recommendations.

Vitamin D and Sleep Regulation: Is there a Role for Vitamin D?

2020 ◽  
Vol 26 (21) ◽  
pp. 2492-2496 ◽  
Author(s):  
Fiammetta Romano ◽  
Giovanna Muscogiuri ◽  
Elea Di Benedetto ◽  
Volha V. Zhukouskaya ◽  
Luigi Barrea ◽  
...  
Keyword(s):  
Vitamin D ◽  
Sleep Disorders ◽  
Vitamin D Deficiency ◽  
Sleep Apnea Syndrome ◽  
Regulatory Mechanisms ◽  
Sleep Regulation ◽  
Vitamin D Receptors ◽  
Obstructive Sleep ◽  
The Impact

Background: Vitamin D exerts multiple pleiotropic effects beyond its role in calcium-phosphate metabolism. Growing evidence suggests an association between hypovitaminosis D and sleep disorders, thus increasing the interest in the role of this vitamin in the regulatory mechanisms of the sleep-wake cycle. Objective: The study aimed to explore and summarize the current knowledge about the role of vitamin D in sleep regulation and the impact of vitamin D deficiency on sleep disorders. Methods: The main regulatory mechanisms of vitamin D on sleep are explained in this study. The literature was scanned to identify clinical trials and correlation studies showing an association between vitamin D deficiency and sleep disorders. Results: Vitamin D receptors and the enzymes that control their activation and degradation are expressed in several areas of the brain involved in sleep regulation. Vitamin D is also involved in the pathways of production of Melatonin, the hormone involved in the regulation of human circadian rhythms and sleep. Furthermore, vitamin D can affect sleep indirectly through non-specific pain disorders, correlated with alterations in sleep quality, such as restless legs syndrome and obstructive sleep apnea syndrome. Conclusions: : Vitamin D has both a direct and an indirect role in the regulation of sleep. Although vitamin D deficiency has been associated to sleep disorders, there is still scant evidence to concretely support the role of vitamin D supplementation in the prevention or treatment of sleep disturbances; indeed, more intervention studies are needed to better clarify these aspects.

scholarly journals Regulation of Rho GTPases by RhoGDIs in Human Cancers

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1037 ◽  
Author(s):  
Cho ◽  
Kim ◽  
Baek ◽  
Kim ◽  
Lee
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Regulatory Mechanisms ◽  
Malignant Phenotype ◽  
Cellular Processes ◽  
Human Cancers

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

scholarly journals System-wide identification and prioritization of enzyme substrates by thermal analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amir Ata Saei ◽  
Christian M. Beusch ◽  
Pierre Sabatier ◽  
Juan Astorga Wells ◽  
Hassan Gharibi ◽  
...  
Keyword(s):  
Thermal Analysis ◽  
Thioredoxin Reductase ◽  
Structural Level ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Enzyme Substrate ◽  
Thioredoxin Reductase 1 ◽  
Enzyme Substrates ◽  
Substrate Proteins

AbstractDespite the immense importance of enzyme–substrate reactions, there is a lack of general and unbiased tools for identifying and prioritizing substrate proteins that are modified by the enzyme on the structural level. Here we describe a high-throughput unbiased proteomics method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that the enzymatic post-translational modification of substrate proteins is likely to change their thermal stability. In our proof-of-concept studies, SIESTA successfully identifies several known and novel substrate candidates for selenoprotein thioredoxin reductase 1, protein kinase B (AKT1) and poly-(ADP-ribose) polymerase-10 systems. Wider application of SIESTA can enhance our understanding of the role of enzymes in homeostasis and disease, opening opportunities to investigate the effect of post-translational modifications on signal transduction and facilitate drug discovery.

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