Corepressor

In genetics and molecular biology, a corepressor is a molecule that represses the expression of genes.[1] In prokaryotes, corepressors are small molecules whereas in eukaryotes, corepressors are proteins. A corepressor does not directly bind to DNA, but instead indirectly regulates gene expression by binding to repressors.

A corepressor downregulates (or represses) the expression of genes by binding to and activating a repressor transcription factor. The repressor in turn binds to a gene's operator sequence (segment of DNA to which a transcription factor binds to regulate gene expression), thereby blocking transcription of that gene.

Corepressor Transcription Factor Complex on Regulatory Element

Function

Prokaryotes

In prokaryotes, the term corepressor is used to denote the activating ligand of a repressor protein. For example, the E. coli tryptophan repressor (TrpR) is only able to bind to DNA and repress transcription of the trp operon when its corepressor tryptophan is bound to it. TrpR in the absence of tryptophan is known as an aporepressor and is inactive in repressing gene transcription.[2] Trp operon encodes enzymes responsible for the synthesis of tryptophan. Hence TrpR provides a negative feedback mechanism that regulates the biosynthesis of tryptophan.

In short tryptophan acts as a corepressor for its own biosynthesis.[3]

Eukaryotes

In eukaryotes, a corepressor is a protein that binds to transcription factors.[4] In the absence of corepressors and in the presence of coactivators, transcription factors upregulate gene expression. Coactivators and corepressors compete for the same binding sites on transcription factors. A second mechanism by which corepressors may repress transcriptional initiation when bound to transcription factor/DNA complexes is by recruiting histone deacetylases which catalyze the removal of acetyl groups from lysine residues. This increases the positive charge on histones which strengthens the electrostatic attraction between the positively charged histones and negatively charged DNA, making the DNA less accessible for transcription.[5][6]

In humans several dozen to several hundred corepressors are known, depending on the level of confidence with which the characterisation of a protein as a corepressors can be made.[7]

Examples of corepressors

NCoR

NCoR (nuclear receptor co-repressor) directly binds to the D and E domains of nuclear receptors and represses their transcriptional activity.[8][9][10] Class I histone deacetylases are recruited by NCoR through SIN3, and NCoR directly binds to class II histone deacetylases.[8][10][11]

Silencing mediator for retinoid and thyroid-hormone receptor

SMRT (silencing mediator of retinoic acid and thyroid hormone receptor), also known as NCoR2, is an alternatively spliced SRC-1(steroid receptor coactivator-1).[8][9] It is negatively and positively affected by MAPKKK (mitogen activated protein kinase kinase kinase) and casein kinase 2 phosphorylation, respectively.[8] SMRT has two major mechanisms: first, similar to NCoR, SMRT also recruits class I histone deacetylases through SIN3 and directly binds to class II histone deacetylases.[8] Second, it binds and sequesters components of the general transcriptional machinery, such as transcription factor II B.[8][10]

Role in biological processes

Corepressors are known to regulate transcription through different activation and inactivation states.[12][13]

NCoR and SMRT act as a corepressor complex to regulate transcription by becoming activated once the ligand is bound.[12][13][14][15] Knockouts of NCoR resulted in embryo death, indicating its importance in erythrocytic, thymic, and neural system development.[15][16]

Mutations in certain corepressors can result in deregulation of signals.[13] SMRT contributes to cardiac muscle development, with knockouts of the complex resulting in less developed muscle and improper development.[13]

NCoR has also been found to be an important checkpoint in processes such as inflammation and macrophage activation.[15]

Recent evidence also suggests the role of corepressor RIP140 in metabolic regulation of energy homeostasis.[14]

Clinical significance

Diseases

Since corepressors participate and regulate a vast range of gene expression, it is not surprising that aberrant corepressor activities can cause diseases.[17]

Acute myeloid leukemia (AML) is a highly lethal blood cancer characterized by uncontrolled myeloid cell growth.[18] Two homologous corepressor genes, BCOR (BCL6 corepressor) and BCORL1, are recurrently mutated in AML patients.[19][20] BCOR works with multiple transcription factors and is known to play vital regulatory roles in embryonic development.[18][19] Clinical results detected BCOR somatic mutations in ~4% of an unselected group of AML patients, and ~17% in a subset of patients who lack known AML-causing mutations.[18][19] Similarly, BCORL1 is a corepressor that regulates cellular processes,[21] and was found to be mutated in ~6% of tested AML patients.[18][20] These studies point out a strong association between corepressor mutations and AML. Further corepressor research may reveal potential therapeutic targets for AML and other diseases.

Therapeutic Potential

Corepressors present many potential avenues for drugs to target a vast range of diseases.[22]

BCL6 upregulation is observed in cancers such as diffuse large B-cell lymphomas (DLBCLs),[23][24][25][26] colorectal cancer,[27][28] and lung cancer.[29][30] BCL-6 corepressor, SMRT, NCoR, and other corepressors are able to interact with and transcriptionally repress BCL6.[23][24][25][26] Small-molecule compounds, such as synthetic peptides that target BCL6 and corepressor interactions,[23][24] as well as other protein-protein interaction inhibitors,[26] have been shown to effectively kill cancer cells.

Activated liver X receptor (LXR) forms a complex with corepressors to suppress the inflammatory response in rheumatoid arthritis, making LXR agonists like GW3965 a potential therapeutic strategy.[31][32] Ursodeoxycholic acid (UDCA), by upregulating the corepressor small heterodimer partner interacting leucine zipper protein (SMILE), inhibits the expression of IL-17, an inflammatory cytokine, and suppresses Th17 cells, both implicated in rheumatoid arthritis.[33][34] This effect is dose-dependent in humans, and UCDA is thought to be another prospective agent of rheumatoid arthritis therapy.[33]

See also

References

  1. ^ Privalsky, Martin L., ed. (2001). Transcriptional Corepressors: Mediators of Eukaryotic Gene Repression. Current Topics in Microbiology and Immunology. Vol. 254. Berlin, Heidelberg: Springer Berlin Heidelberg. doi:10.1007/978-3-662-10595-5. ISBN 978-3-642-08709-7. S2CID 8922796.
  2. ^ Evans PD, Jaseja M, Jeeves M, Hyde EI (December 1996). "NMR studies of the Escherichia coli Trp repressor.trpRs operator complex". Eur. J. Biochem. 242 (3): 567–75. doi:10.1111/j.1432-1033.1996.0567r.x. PMID 9022683.
  3. ^ Foster JB, Slonczewski J (2010). Microbiology: An Evolving Science (Second ed.). New York: W. W. Norton & Company. ISBN 978-0-393-93447-2.
  4. ^ Jenster G (August 1998). "Coactivators and corepressors as mediators of nuclear receptor function: an update". Mol. Cell. Endocrinol. 143 (1–2): 1–7. doi:10.1016/S0303-7207(98)00145-2. PMID 9806345. S2CID 26244186.
  5. ^ Lazar MA (2003). "Nuclear receptor corepressors". Nucl Recept Signal. 1: e001. doi:10.1621/nrs.01001. PMC 1402229. PMID 16604174.
  6. ^ Goodson M, Jonas BA, Privalsky MA (2005). "Corepressors: custom tailoring and alterations while you wait". Nucl Recept Signal. 3 (Oct 21): e003. doi:10.1621/nrs.03003. PMC 1402215. PMID 16604171.
  7. ^ Schaefer U, Schmeier S, Bajic VB (January 2011). "TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins". Nucleic Acids Res. 39 (Database issue): D106–10. doi:10.1093/nar/gkq945. PMC 3013796. PMID 20965969.
  8. ^ a b c d e f Bolander, Franklyn F. (2004), "Hormonally Regulated Transcription Factors", Molecular Endocrinology, Elsevier, pp. 387–443, doi:10.1016/b978-012111232-5/50013-0, ISBN 978-0-12-111232-5, retrieved 2020-10-25
  9. ^ a b Chinnadurai, G (February 2002). "CtBP, an Unconventional Transcriptional Corepressor in Development and Oncogenesis". Molecular Cell. 9 (2): 213–224. doi:10.1016/S1097-2765(02)00443-4. PMID 11864595.
  10. ^ a b c Kammer, Gary M. (2004), "Estrogen, Signal Transduction, and Systemic Lupus Erythematosus: Molecular Mechanisms", Principles of Gender-Specific Medicine, Elsevier, pp. 1082–1092, doi:10.1016/b978-012440905-7/50375-3, ISBN 978-0-12-440905-7, retrieved 2020-10-25
  11. ^ Kadamb, Rama; Mittal, Shilpi; Bansal, Nidhi; Batra, Harish; Saluja, Daman (August 2013). "Sin3: Insight into its transcription regulatory functions". European Journal of Cell Biology. 92 (8–9): 237–246. doi:10.1016/j.ejcb.2013.09.001. PMID 24189169.
  12. ^ a b Rosenfeld, M. G. (2006-06-01). "Sensors and signals: a coactivator/corepressor/epigenetic code for integrating signal-dependent programs of transcriptional response". Genes & Development. 20 (11): 1405–1428. doi:10.1101/gad.1424806. ISSN 0890-9369. PMID 16751179.
  13. ^ a b c d Battaglia, Sebastiano; Maguire, Orla; Campbell, Moray J. (2010). "Transcription factor co-repressors in cancer biology: roles and targeting". International Journal of Cancer. 126 (11): 2511–9. doi:10.1002/ijc.25181. PMC 2847647. PMID 20091860.
  14. ^ a b Christian, Mark; White, Roger; Parker, Malcolm G. (August 2006). "Metabolic regulation by the nuclear receptor corepressor RIP140". Trends in Endocrinology & Metabolism. 17 (6): 243–250. doi:10.1016/j.tem.2006.06.008. PMID 16815031. S2CID 45870845.
  15. ^ a b c Ogawa, S.; Lozach, J.; Jepsen, K.; Sawka-Verhelle, D.; Perissi, V.; Sasik, R.; Rose, D. W.; Johnson, R. S.; Rosenfeld, M. G.; Glass, C. K. (2004-10-05). "A nuclear receptor corepressor transcriptional checkpoint controlling activator protein 1-dependent gene networks required for macrophage activation". Proceedings of the National Academy of Sciences. 101 (40): 14461–14466. Bibcode:2004PNAS..10114461O. doi:10.1073/pnas.0405786101. ISSN 0027-8424. PMC 521940. PMID 15452344.
  16. ^ Jepsen, Kristen; Hermanson, Ola; Onami, Thandi M; Gleiberman, Anatoli S; Lunyak, Victoria; McEvilly, Robert J; Kurokawa, Riki; Kumar, Vivek; Liu, Forrest; Seto, Edward; Hedrick, Stephen M (September 2000). "Combinatorial Roles of the Nuclear Receptor Corepressor in Transcription and Development". Cell. 102 (6): 753–763. doi:10.1016/S0092-8674(00)00064-7. PMID 11030619. S2CID 15645977.
  17. ^ Privalsky, Martin L. (March 2004). "The Role of Corepressors in Transcriptional Regulation by Nuclear Hormone Receptors". Annual Review of Physiology. 66 (1): 315–360. doi:10.1146/annurev.physiol.66.032802.155556. ISSN 0066-4278. PMID 14977406.
  18. ^ a b c d Tiacci, E.; Grossmann, V.; Martelli, M. P.; Kohlmann, A.; Haferlach, T.; Falini, B. (2011-12-30). "The corepressors BCOR and BCORL1: two novel players in acute myeloid leukemia". Haematologica. 97 (1): 3–5. doi:10.3324/haematol.2011.057901. ISSN 0390-6078. PMC 3248923. PMID 22210327.
  19. ^ a b c Grossmann, Vera; Tiacci, Enrico; Holmes, Antony B.; Kohlmann, Alexander; Martelli, Maria Paola; Kern, Wolfgang; Spanhol-Rosseto, Ariele; Klein, Hans-Ulrich; Dugas, Martin; Schindela, Sonja; Trifonov, Vladimir (2011-12-01). "Whole-exome sequencing identifies somatic mutations of BCOR in acute myeloid leukemia with normal karyotype". Blood. 118 (23): 6153–6163. doi:10.1182/blood-2011-07-365320. ISSN 0006-4971. PMID 22012066.
  20. ^ a b Li, Meng; Collins, Roxane; Jiao, Yuchen; Ouillette, Peter; Bixby, Dale; Erba, Harry; Vogelstein, Bert; Kinzler, Kenneth W.; Papadopoulos, Nickolas; Malek, Sami N. (2011-11-24). "Somatic mutations in the transcriptional corepressor gene BCORL1 in adult acute myelogenous leukemia". Blood. 118 (22): 5914–5917. doi:10.1182/blood-2011-05-356204. ISSN 0006-4971. PMC 3228503. PMID 21989985.
  21. ^ Pagan, Julia K.; Arnold, Jeremy; Hanchard, Kim J.; Kumar, Raman; Bruno, Tiziana; Jones, Mathew J. K.; Richard, Derek J.; Forrest, Alistair; Spurdle, Amanda; Verdin, Eric; Crossley, Merlin (2007-03-22). "A Novel Corepressor, BCoR-L1, Represses Transcription through an Interaction with CtBP". Journal of Biological Chemistry. 282 (20): 15248–15257. doi:10.1074/jbc.m700246200. ISSN 0021-9258. PMID 17379597.
  22. ^ Vaiopoulos, Aristeidis G.; Kostakis, Ioannis D.; Athanasoula, Kalliopi Ch.; Papavassiliou, Athanasios G. (June 2012). "Targeting transcription factor corepressors in tumor cells". Cellular and Molecular Life Sciences. 69 (11): 1745–1753. doi:10.1007/s00018-012-0986-5. ISSN 1420-682X. PMC 11114811. PMID 22527719. S2CID 16407925.
  23. ^ a b c Cerchietti, Leandro C.; Ghetu, Alexandru F.; Zhu, Xiao; Da Silva, Gustavo F.; Zhong, Shijun; Matthews, Marilyn; Bunting, Karen L.; Polo, Jose M.; Farès, Christophe; Arrowsmith, Cheryl H.; Yang, Shao Ning (April 2010). "A Small-Molecule Inhibitor of BCL6 Kills DLBCL Cells In Vitro and In Vivo". Cancer Cell. 17 (4): 400–411. doi:10.1016/j.ccr.2009.12.050. PMC 2858395. PMID 20385364.
  24. ^ a b c Cerchietti, Leandro C.; Yang, Shao Ning; Shaknovich, Rita; Hatzi, Katerina; Polo, Jose M.; Chadburn, Amy; Dowdy, Steven F.; Melnick, Ari (2009-04-09). "A peptomimetic inhibitor of BCL6 with potent antilymphoma effects in vitro and in vivo". Blood. 113 (15): 3397–3405. doi:10.1182/blood-2008-07-168773. ISSN 0006-4971. PMC 2668844. PMID 18927431.
  25. ^ a b Parekh, Samir; Privé, Gilbert; Melnick, Ari (January 2008). "Therapeutic targeting of the BCL6 oncogene for diffuse large B-cell lymphomas". Leukemia & Lymphoma. 49 (5): 874–882. doi:10.1080/10428190801895345. ISSN 1042-8194. PMC 2748726. PMID 18452090.
  26. ^ a b c Yasui, Takeshi; Yamamoto, Takeshi; Sakai, Nozomu; Asano, Kouhei; Takai, Takafumi; Yoshitomi, Yayoi; Davis, Melinda; Takagi, Terufumi; Sakamoto, Kotaro; Sogabe, Satoshi; Kamada, Yusuke (September 2017). "Discovery of a novel B-cell lymphoma 6 (BCL6)–corepressor interaction inhibitor by utilizing structure-based drug design". Bioorganic & Medicinal Chemistry. 25 (17): 4876–4886. doi:10.1016/j.bmc.2017.07.037. PMID 28760529.
  27. ^ Sena, Paola; Mariani, Francesco; Benincasa, Marta; De Leon, Maurizio Ponz; Di Gregorio, Carmela; Mancini, Stefano; Cavani, Francesco; Smargiassi, Alberto; Palumbo, Carla; Roncucci, Luca (January 2014). "Morphological and quantitative analysis of BCL6 expression in human colorectal carcinogenesis". Oncology Reports. 31 (1): 103–110. doi:10.3892/or.2013.2846. hdl:11380/1011113. ISSN 1021-335X. PMID 24220798.
  28. ^ Sun, Naihui; Zhang, Liang; Zhang, Chongguang; Yuan, Yuan (December 2020). "miR-144-3p inhibits cell proliferation of colorectal cancer cells by targeting BCL6 via inhibition of Wnt/β-catenin signaling". Cellular & Molecular Biology Letters. 25 (1): 19. doi:10.1186/s11658-020-00210-3. ISSN 1425-8153. PMC 7079415. PMID 32206063.
  29. ^ Deb, Dhruba; Rajaram, Satwik; Larsen, Jill E.; Dospoy, Patrick D.; Marullo, Rossella; Li, Long Shan; Avila, Kimberley; Xue, Fengtian; Cerchietti, Leandro; Minna, John D.; Altschuler, Steven J. (2017-06-01). "Combination Therapy Targeting BCL6 and Phospho-STAT3 Defeats Intratumor Heterogeneity in a Subset of Non–Small Cell Lung Cancers". Cancer Research. 77 (11): 3070–3081. doi:10.1158/0008-5472.CAN-15-3052. ISSN 0008-5472. PMC 5489259. PMID 28377453.
  30. ^ Sun, Chengcao; Li, Shujun; Yang, Cuili; Xi, Yongyong; Wang, Liang; Zhang, Feng; Li, Dejia (February 2016). "MicroRNA-187-3p mitigates non-small cell lung cancer (NSCLC) development through down-regulation of BCL6". Biochemical and Biophysical Research Communications. 471 (1): 82–88. doi:10.1016/j.bbrc.2016.01.175. PMID 26845350.
  31. ^ Venteclef, N.; Jakobsson, T.; Ehrlund, A.; Damdimopoulos, A.; Mikkonen, L.; Ellis, E.; Nilsson, L.-M.; Parini, P.; Janne, O. A.; Gustafsson, J.-A.; Steffensen, K. R. (2010-02-15). "GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions of LRH-1 and LXR in the hepatic acute phase response". Genes & Development. 24 (4): 381–395. doi:10.1101/gad.545110. ISSN 0890-9369. PMC 2816737. PMID 20159957.
  32. ^ Yoon, Chong-Hyeon; Kwon, Yong-Jin; Lee, Sang-Won; Park, Yong-Beom; Lee, Soo-Kon; Park, Min-Chan (January 2013). "Activation of Liver X Receptors Suppresses Inflammatory Gene Expressions and Transcriptional Corepressor Clearance in Rheumatoid Arthritis Fibroblast Like Synoviocytes". Journal of Clinical Immunology. 33 (1): 190–199. doi:10.1007/s10875-012-9799-4. ISSN 0271-9142. PMID 22990668. S2CID 15965750.
  33. ^ a b Lee, Eun-Jung; Kwon, Jeong-Eun; Park, Min-Jung; Jung, Kyung-Ah; Kim, Da-Som; Kim, Eun-Kyung; Lee, Seung Hoon; Choi, Jong Young; Park, Sung-Hwan; Cho, Mi-La (August 2017). "Ursodeoxycholic acid attenuates experimental autoimmune arthritis by targeting Th17 and inducing pAMPK and transcriptional corepressor SMILE". Immunology Letters. 188: 1–8. doi:10.1016/j.imlet.2017.05.011. PMID 28539269.
  34. ^ Sarkar, Sujata; Fox, David A. (May 2010). "Targeting IL-17 and Th17 Cells in Rheumatoid Arthritis". Rheumatic Disease Clinics of North America. 36 (2): 345–366. doi:10.1016/j.rdc.2010.02.006. PMID 20510238.

Read other articles:

Negeri Sembilan FC

Negeri Sembilan FCJulukanSi Rusa The JangsBerdiri1923StadionStadion Tuanku Abdul Rahman, Negeri Sembilan(Kapasitas: 40.000[1])PemilikNegeri Sembilan Football ClubKetuaMohammad HassanPelatihGary Michael PhillipsLigaLiga Utama Malaysia2019Ke-6Situs webSitus web resmi klub Kostum kandang Kostum tandang Negeri Sembilan FC adalah klub sepak bola yang berlaga di Liga Utama Malaysia. Klub ini bermarkas di Seremban, Negeri Sembilan. Klub ini berganti nama menjadi NS Matrix FC saat dimula...

 

 

العلاقات الإثيوبية السورية

العلاقات الإثيوبية السورية إثيوبيا سوريا   إثيوبيا   سوريا تعديل مصدري - تعديل   العلاقات الإثيوبية السورية هي العلاقات الثنائية التي تجمع بين إثيوبيا وسوريا.[1][2][3][4][5] مقارنة بين البلدين هذه مقارنة عامة ومرجعية للدولتين: وجه المقارنة إثي�...

 

 

Александр II (царь Кахетии)

У этого термина существуют и другие значения, см. Александр II (значения). Александр IIალექსანდრე II Царь Кахети 1574 — 1601 Предшественник Леван Преемник Давид I Царь Кахети 1602 — 1605 Предшественник Давид I Преемник Константин I Рождение 1527(1527)Тифлис, Картлийское царств...

Proscription

Cet article est une ébauche concernant la Rome antique. Vous pouvez partager vos connaissances en l’améliorant (comment ?) selon les recommandations des projets correspondants. Sylla fait afficher la liste des proscrits. Gravure. Dessin de Silvestre David Mirys. Numéro 138 dans Figures de l'histoire de la république romaine accompagnées d'un précis historique, Paris, an VIII. Une proscription (du latin pro scribo qui signifie « afficher ») est une condamnation arbitr...

 

 

Desert Dolphin Skatepark

Skatepark in Khempur, Rajasthan, India Desert Dolphin SkateparkTypeSkateparkLocationKhempur, RajasthanNearest cityUdaipurCoordinates24°45′07″N 74°01′51″E / 24.7519°N 74.0307°E / 24.7519; 74.0307.Area14,500 Sq. Ft.OpenedSeptember 2018Operated byLiving Grace FoundationTerrainConcrete Desert Dolphin Skatepark was constructed as a part of the Netflix original film Skater Girl and is now a free public skatepark located in Khempur, Rajasthan. It is one ...

 

 

CERES (satellite)

French military satellite program CERESCERES satelliteMission typeSIGINTOperatorCNES / DGACOSPAR ID2021-105A2021-105B2021-105CSATCAT no.494644946549466 Spacecraft propertiesBusEliteBusManufacturerThales Alenia Space (bus),Airbus Defence and Space (payload)Launch mass516 kg (1,138 lb) (each) Start of missionLaunch date16 November 2021, 09:27:55 UTC[1]RocketVega VV20Launch siteCentre Spatial Guyanais,Kourou, ELA-1ContractorArianespace Orbital parametersReference systemGeo...

VFC-111

For previous US Navy fighter squadrons designated Sundowners, see VF-111 and VF-111 (1956-1995). Fighter Squadron Composite 111A squadron F-5N Tiger II at NAS Key West in 2020Active1 November 2006 – present[1]Country United StatesBranch United States NavyTypeAdversary SquadronPart of United States Navy Reserve Naval Air Force Reserve Tactical Support Wing Garrison/HQ Naval Air Station Key WestNickname(s)Sun DownersMotto(s)Semper Confidens, Numquam Elatus[citation ...

 

 

Facial lymph nodes

Facial lymph nodesThe lymphatics of the face.Facial lymph nodes labelled 8 - 12DetailsSystemLymphatic systemIdentifiersLatinnodi lymphoidei facialesFMA233946Anatomical terminology[edit on Wikidata] The facial lymph nodes comprise three groups: (a) infraorbital or maxillary, scattered over the infraorbital region from the groove between the nose and cheek to the zygomatic arch; (b) buccinator, one or more placed on the buccinator muscle opposite the angle of the mouth; (c) supramandibular,...

 

 

Tango-class submarine

Soviet diesel-electric submarine class This article includes a list of references, related reading, or external links, but its sources remain unclear because it lacks inline citations. Please help improve this article by introducing more precise citations. (January 2013) (Learn how and when to remove this message) A Tango-class submarine in the North Atlantic. Class overview NameTango class (Project 641B) BuildersGorky Operators Soviet Navy Preceded byFoxtrot class Succeeded byKilo ...

Temperate broadleaf and mixed forests

Biome Extent of temperate broadleaf and mixed forests An example of temperate broadleaf and mixed forest in La Mauricie National Park, Quebec. Temperate broadleaf and mixed forest is a temperate climate terrestrial habitat type defined by the World Wide Fund for Nature, with broadleaf tree ecoregions, and with conifer and broadleaf tree mixed coniferous forest ecoregions.[1] These forests are richest and most distinctive in central China and eastern North America, with some other glob...

 

 

Hauteville-sur-Mer

Pour les articles homonymes, voir Hauteville. Hauteville-sur-Mer La digue de Hauteville-sur-Mer Plage, promenade longue de 1,7 km. Administration Pays France Région Normandie Département Manche Arrondissement Coutances Intercommunalité Communauté de communes Coutances Mer et Bocage Maire Mandat Jean-René Binet (LR) 2020-2026 Code postal 50590 Code commune 50231 Démographie Gentilé Hautais Populationmunicipale 700 hab. (2021 ) Densité 211 hab./km2 Géographie Coordonné...

 

 

Louis Slotin

Canadian physicist and chemist Louis SlotinSlotin's Los Alamos badge photoBornLouis Alexander Slotin(1910-12-01)1 December 1910Winnipeg, Manitoba, CanadaDied30 May 1946(1946-05-30) (aged 35)Los Alamos National Laboratory, Los Alamos, New Mexico, U.S.Cause of deathAcute radiation syndromeEducationUniversity of Manitoba (BSc, MSc)King's College London (PhD)Occupation(s)Physicist and chemistKnown forCriticality tests on Plutonium & nuclear weapons assembling, the Dollar unit o...

Alex Jones

American radio host and conspiracy theorist (born 1974) This article is about the radio show host. For other people with the same name, see Alex Jones (disambiguation). Alex JonesJones in 2017BornAlexander Emerick Jones (1974-02-11) February 11, 1974 (age 50)Dallas, Texas, U.S.OccupationRadio hostKnown forInfoWarsThe Alex Jones ShowConspiracy theoriesSandy Hook shooting litigationSpouses Kelly Jones ​ ​(m. 2007; div. 2015)​ Erika Wulff...

 

 

Stadio Atleti Azzurri d'Italia

Football stadium Gewiss StadiumStadio di BergamoThe outside of the stadium in 2020.Former namesStadio Mario Brumana (1928–1945)Stadio ComunaleStadio Atleti Azzurri d'ItaliaLocationBergamo, ItalyCoordinates45°42′32″N 9°40′51″E / 45.70889°N 9.68083°E / 45.70889; 9.68083OwnerStadio Atalanta S.r.l.Capacity21,747[1]Field size105 m × 68 m (344 ft × 223 ft)SurfaceFLexGrass Vertix hybrid grassConstructionBroke ground1927Ope...

 

 

جزيرة سانتا روزا (كاليفورنيا)

جزيرة سانتا روزا (كاليفورنيا)   معلومات جغرافية الإحداثيات 33°57′00″N 120°06′03″W / 33.950003°N 120.1009639°W / 33.950003; -120.1009639   [1] [2] الأرخبيل جزر القناة في كاليفورنيا  المسطح المائي المحيط الهادئ  المساحة 83.12 ميل مربع  الطول 26 كيلومتر  العرض 17 كيلومتر  ...

بوابة:علم البيئة

اختصاراتب:ع ب ثقافة — جغرافيا — تاريخ — علوم — مجتمع — تقانة — رياضة قائمة البوابات علم البيئة هو الدراسة العلمية لتوزع وتلاؤم الكائنات الحية مع بيئاتها المحيطة وكيف تتأثر هذه الكائنات بالعلاقات المتبادلة بين الأحياء كافة وبين بيئاتها المحيطة. بيئة الكائن الحي تتضمن ال...

 

 

Constitution Day (Denmark)

National holiday in Denmark GrundlovsdagConstitution Day celebrations in Frederiksberg Gardens. Drawn by Erik Henningsen, 1882.Also calledConstitution DayObserved byDanesTypeNationalSignificanceAnniversary of the Danish constitutionCelebrationsSpeeches by politiciansDate5 JuneNext time5 June 2025 (2025-06-05)Frequencyannual Constitution Day (Danish: Grundlovsdag) is observed in Denmark on 5 June.[1][2] The day honours the Constitution of Denmark, as both the fir...

 

 

Music of Serbia

Part of a series on theCulture of Serbia History Middle Ages Monarchs People Languages Serbian language Old Serbian Traditions Dress Kinship Mythology and folklore Cuisine Festivals Religion Christianity Serbian Orthodox Church Patriarch Roman Catholicism Protestantism Hinduism Islam Judaism Art Architecture Music Composers (list) Painters (category) Sculptors (category) Heraldry Literature Comics Epic poetry Writers (category) Music and performing arts Dances Theatres (category) Actors (cat...

Honda X4

Honda X4Costruttore Honda Produzionedal 1997 al 2003 Sostituisce laHonda CB Stessa famigliaHonda CB 1300 Modelli similiYamaha V-Max[1] Manuale La Honda X4 (scritto anche X-4) è una motocicletta prodotto dalla casa motociclistica giapponese Honda dal 1997 al 2003. Indice 1 Descrizione 1.1 X4 LD 2 Caratteristiche tecniche 3 Note 4 Altri progetti 5 Collegamenti esterni Descrizione La X4 è una cruiser, dotata di un propulsore da 1284 cm³ a quattro cilindri con distribuzione b...

 

 

Riciclaggio dei rifiuti

Disambiguazione – Riciclo rimanda qui. Se stai cercando il riciclo nell'ambito degli impianti chimici, vedi Corrente di ricircolo. Disambiguazione – Riciclaggio rimanda qui. Se stai cercando altri significati, vedi Riciclaggio di denaro. Il simbolo internazionale per i materiali riciclabili Per il riciclo dei rifiuti si intende l'insieme di strategie e metodologie volte a recuperare materiali utili dai rifiuti al fine di riutilizzarli anziché smaltirli direttamente in di...