Controlling Gene Expression in Hypoxia: Comparison
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Please note this is a comparison between Version 2 by Lily Guo and Version 1 by Michael Batie.

Hypoxia—reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OGDs in the control of gene expression in response to hypoxia and their relevance to human biology and health. 

  • hypoxia
  • 2-OG dioxygenases
  • HIF
  • transcription
  • trmas
  • translation
  • chromatin
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  110. Lindgren, A.M.; Hoyos, T.; Talkowski, M.E.; Hanscom, C.; Blumenthal, I.; Chiang, C.; Ernst, C.; Pereira, S.; Ordulu, Z.; Clericuzio, C.; et al. Haploinsufficiency of KDM6A is associated with severe psychomotor retardation, global growth restriction, seizures and cleft palate. Hum. Genet. 2013, 132, 537–552, doi:10.1007/s00439-013-1263-x.
  111. Dunwoodie, S.L. The role of hypoxia in development of the Mammalian embryo. Dev Cell. 2009, 17, 755–773, doi:10.1016/j.devcel.2009.11.008.
  112. Huang, X.; Zhang, S.; Qi, H.; Wang, Z.; Chen, H.W.; Shao, J.; Shen, J. JMJD5 interacts with p53 and negatively regulates p53 function in control of cell cycle and proliferation. Biochim. Biophys. Acta 2015, 1853, 2286–2295, doi:10.1016/j.bbamcr.2015.05.026.
  113. Ishimura, A.; Terashima, M.; Tange, S.; Suzuki, T. Jmjd5 functions as a regulator of p53 signaling during mouse embryogenesis. Cell Tissue Res. 2016, 363, 723–733, doi:10.1007/s00441-015-2276-7.
  114. Markolovic, S.; Zhuang, Q.; Wilkins, S.E.; Eaton, C.D.; Abboud, M.I.; Katz, M.J.; McNeil, H.E.; Lesniak, R.K.; Hall, C.; Struwe, W.B.; et al. The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases. Nat. Chem. Biol. 2018, 14, 688–695, doi:10.1038/s41589-018-0071-y.
  115. Lu, T.; Jackson, M.W.; Wang, B.; Yang, M.; Chance, M.R.; Miyagi, M.; Gudkov, A.V.; Stark, G.R. Regulation of NF-kappaB by NSD1/FBXL11-dependent reversible lysine methylation of p65. Proc. Natl. Acad. Sci. USA 2010, 107, 46–51, doi:10.1073/pnas.0912493107.
  116. Ramadoss, S.; Guo, G.; Wang, C.Y. Lysine demethylase KDM3A regulates breast cancer cell invasion and apoptosis by targeting histone and the non-histone protein p53. Oncogene 2017, 36, 47–59, doi:10.1038/onc.2016.174.
  117. Ponnaluri, V.K.; Vavilala, D.T.; Putty, S.; Gutheil, W.G.; Mukherji, M. Identification of non-histone substrates for JMJD2A-C histone demethylases. Biochem. Biophys. Res. Commun. 2009, 390, 280–284, doi:10.1016/j.bbrc.2009.09.107.
  118. Walport, L.J.; Hopkinson, R.J.; Chowdhury, R.; Schiller, R.; Ge, W.; Kawamura, A.; Schofield, C.J. Arginine demethylation is catalysed by a subset of JmjC histone lysine demethylases. Nat. Commun. 2016, 7, 11974, doi:10.1038/ncomms11974.
  119. Meyer, K.D.; Patil, D.P.; Zhou, J.; Zinoviev, A.; Skabkin, M.A.; Elemento, O.; Pestova, T.V.; Qian, S.B.; Jaffrey, S.R. 5' UTR m(6)A Promotes Cap-Independent Translation. Cell 2015, 163, 999–1010, doi:10.1016/j.cell.2015.10.012.
  120. Stenson, P.D.; Mort, M.; Ball, E.V.; Shaw, K.; Phillips, A.; Cooper, D.N. The Human Gene Mutation Database: Building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Hum. Genet. 2014, 133, 1–9, doi:10.1007/s00439-013-1358-4.
  121. Ang, S.O.; Chen, H.; Hirota, K.; Gordeuk, V.R.; Jelinek, J.; Guan, Y.; Liu, E.; Sergueeva, A.I.; Miasnikova, G.Y.; Mole, D.; et al. Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. Nat. Genet. 2002, 32, 614–621, doi:10.1038/ng1019.
  122. Gordeuk, V.R.; Sergueeva, A.I.; Miasnikova, G.Y.; Okhotin, D.; Voloshin, Y.; Choyke, P.L.; Butman, J.A.; Jedlickova, K.; Prchal, J.T.; Polyakova, L.A. Congenital disorder of oxygen sensing: Association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors. Blood 2004, 103, 3924–3932, doi:10.1182/blood-2003-07-2535.
  123. Smith, T.G.; Brooks, J.T.; Balanos, G.M.; Lappin, T.R.; Layton, D.M.; Leedham, D.L.; Liu, C.; Maxwell, P.H.; McMullin, M.F.; McNamara, C.J.; et al. Mutation of von Hippel-Lindau tumour suppressor and human cardiopulmonary physiology. PLoS Med. 2006, 3, e290, doi:10.1371/journal.pmed.0030290.
  124. Rasmussen, K.D.; Helin, K. Role of TET enzymes in DNA methylation, development, and cancer. Genes Dev. 2016, 30, 733–750, doi:10.1101/gad.276568.115.
  125. Delhommeau, F.; Dupont, S.; Della Valle, V.; James, C.; Trannoy, S.; Masse, A.; Kosmider, O.; Le Couedic, J.P.; Robert, F.; Alberdi, A.; et al. Mutation in TET2 in myeloid cancers. N. Engl. J. Med. 2009, 360, 2289–2301, doi:10.1056/NEJMoa0810069.
  126. Lederer, D.; Grisart, B.; Digilio, M.C.; Benoit, V.; Crespin, M.; Ghariani, S.C.; Maystadt, I.; Dallapiccola, B.; Verellen-Dumoulin, C. Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome. Am. J. Hum. Genet. 2012, 90, 119–124, doi:10.1016/j.ajhg.2011.11.021.
  127. Yang, P.; Tan, H.; Xia, Y.; Yu, Q.; Wei, X.; Guo, R.; Peng, Y.; Chen, C.; Li, H.; Mei, L.; et al. De novo exonic deletion of KDM6A in a Chinese girl with Kabuki syndrome: A case report and brief literature review. Am. J. Med. Genet. A 2016, 170, 1613–1621, doi:10.1002/ajmg.a.37634.
  128. Lindgren, A.M.; Hoyos, T.; Talkowski, M.E.; Hanscom, C.; Blumenthal, I.; Chiang, C.; Ernst, C.; Pereira, S.; Ordulu, Z.; Clericuzio, C.; et al. Haploinsufficiency of KDM6A is associated with severe psychomotor retardation, global growth restriction, seizures and cleft palate. Hum. Genet. 2013, 132, 537–552, doi:10.1007/s00439-013-1263-x.
  129. Dunwoodie, S.L. The role of hypoxia in development of the Mammalian embryo. Dev Cell. 2009, 17, 755–773, doi:10.1016/j.devcel.2009.11.008.
  130. Banka, S.; Lederer, D.; Benoit, V.; Jenkins, E.; Howard, E.; Bunstone, S.; Kerr, B.; McKee, S.; Lloyd, I.C.; Shears, D.; et al. Novel KDM6A (UTX) mutations and a clinical and molecular review of the X-linked Kabuki syndrome (KS2). Clin. Genet. 2015, 87, 252–258, doi:10.1111/cge.12363.
  131. Van Laarhoven, P.M.; Neitzel, L.R.; Quintana, A.M.; Geiger, E.A.; Zackai, E.H.; Clouthier, D.E.; Artinger, K.B.; Ming, J.E.; Shaikh, T.H. Kabuki syndrome genes KMT2D and KDM6A: Functional analyses demonstrate critical roles in craniofacial, heart and brain development. Hum. Mol. Genet. 2015, 24, 4443–4453, doi:10.1093/hmg/ddv180.
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