Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-23T11:48:50.992Z Has data issue: false hasContentIssue false

Regulatory role of JMJD6 in placental development

Published online by Cambridge University Press:  19 September 2022

Xiaoli Shen*
Affiliation:
Chongqing Reproductive and Genetics Institute, Chongqing Health Center for Women and Children; Women and Children's Hospital of Chongqing Medical University, Chongqing, PR China
Christian De Geyter
Affiliation:
Reproductive Medicine and Gynecological Endocrinology (RME), University Hospital, University of Basel, Basel, Switzerland
Hong Zhang
Affiliation:
Department of Biomedicine, University Hospital, University of Basel, Basel, Switzerland
Guoning Huang
Affiliation:
Chongqing Reproductive and Genetics Institute, Chongqing Health Center for Women and Children; Women and Children's Hospital of Chongqing Medical University, Chongqing, PR China
*
Author for correspondence: Xiaoli Shen, E-mail: [email protected]

Abstract

Correct placental development and function are critical to both the mother's and the foetus' health during pregnancy. Placental function depends on the correct development of the vascular network, which requires proper angiogenesis. Impaired angiogenesis in the placenta can induce foetal growth restriction, preeclampsia, and even foetal death. Placental angiogenesis is finely controlled by ubiquitous and pregnancy-specific angiogenic factors. Jumonji domain-containing protein 6 (JMJD6) is a Fe (II)- and 2-oxoglutarate (2OG)-dependent oxygenase that catalyses arginine demethylation and lysine hydroxylation of histone and non-histone peptides. JMJD6 has been implicated in embryonic development, cellular proliferation and migration, self-tolerance induction in the thymus, and adipocyte differentiation. In this review we present JMJD6's structure and activity, as well as its role in angiogenesis, oxygen sensing, and adverse pregnancy outcomes related to placental development. Understanding the interaction between JMJD6 and other placental factors may identify potential therapeutic targets for correcting abnormal placental angiogenesis and function.

Type
Short Review
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Carter, AM (2012) Evolution of placental function in mammals: the molecular basis of gas and nutrient transfer, hormone secretion, and immune responses. Physiological Reviews 92, 15431576.CrossRefGoogle ScholarPubMed
Saben, J et al. (2014) Maternal obesity is associated with a lipotoxic placental environment. Placenta 35, 171177.CrossRefGoogle ScholarPubMed
Mehendale, R et al. (2007) Placental angiogenesis markers sFlt-1 and PlGF: response to cigarette smoke. American Journal of Obstetrics and Gynecology 197, 363 e361365.CrossRefGoogle ScholarPubMed
Khalil, A et al. (2008) Effect of antihypertensive therapy with alpha methyldopa on levels of angiogenic factors in pregnancies with hypertensive disorders. PLoS One 3, e2766.CrossRefGoogle ScholarPubMed
Pereira, RD et al. (2015) Angiogenesis in the placenta: the role of reactive oxygen species signaling. Biomed Research International 2015, 814543.CrossRefGoogle ScholarPubMed
Pijnenborg, R et al. (1991) Placental bed spiral arteries in the hypertensive disorders of pregnancy. British Journal of Obstetrics and Gynaecology 98, 648655.CrossRefGoogle ScholarPubMed
Barut, F et al. (2010) Intrauterine growth restriction and placental angiogenesis. Diagnostic Pathology 5, 24.CrossRefGoogle ScholarPubMed
Pinar, H and Carpenter, M (2010) Placenta and umbilical cord abnormalities seen with stillbirth. Clinical Obstetrics and Gynecology 53, 656672.CrossRefGoogle ScholarPubMed
Kovo, M, Schreiber, L and Bar, J (2013) Placental vascular pathology as a mechanism of disease in pregnancy complications. Thrombosis Research 131(suppl. 1), S18S21.CrossRefGoogle ScholarPubMed
Kristensen, J et al. (2005) Pre-pregnancy weight and the risk of stillbirth and neonatal death. BJOG: An International Journal of Obstetrics and Gynaecology 112, 403408.CrossRefGoogle ScholarPubMed
Longtine, MS and Nelson, DM (2011) Placental dysfunction and fetal programming: the importance of placental size, shape, histopathology, and molecular composition. Seminars in Reproductive Medicine 29, 187196.CrossRefGoogle ScholarPubMed
Reynolds, LP et al. (2006) Evidence for altered placental blood flow and vascularity in compromised pregnancies. Journal of Physiology 572, 5158.CrossRefGoogle ScholarPubMed
Klagsbrun, M and D'Amore, PA (1991) Regulators of angiogenesis. Annual Review of Physiology 53, 217239.CrossRefGoogle ScholarPubMed
Ferrara, N and Davis-Smyth, T (1997) The biology of vascular endothelial growth factor. Endocrine Reviews 18, 425.CrossRefGoogle ScholarPubMed
Hanahan, D (1997) Signaling vascular morphogenesis and maintenance. Science (New York, N.Y.) 277, 4850.CrossRefGoogle ScholarPubMed
Neufeld, G et al. (1999) Vascular endothelial growth factor (VEGF) and its receptors. FASEB Journal 13, 922.CrossRefGoogle ScholarPubMed
Levine, RJ et al. (2004) Circulating angiogenic factors and the risk of preeclampsia. New England Journal of Medicine 350, 672683.CrossRefGoogle ScholarPubMed
Cargnello, M and Roux, PP (2011) Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiology and Molecular Biology Reviews 75, 5083.CrossRefGoogle ScholarPubMed
Vanhaesebroeck, B et al. (1997) Phosphoinositide 3-kinases: a conserved family of signal transducers. Trends in Biochemical Sciences 22, 267272.CrossRefGoogle ScholarPubMed
Cooke, JP (2003) NO and angiogenesis. Atherosclerosis Supplements 4, 5360.CrossRefGoogle ScholarPubMed
Sharma, S, Kelly, TK and Jones, PA (2010) Epigenetics in cancer. Carcinogenesis 31, 2736.CrossRefGoogle ScholarPubMed
Poulard, C, Corbo, L and Le Romancer, M (2016) Protein arginine methylation/demethylation and cancer. Oncotarget 7, 6753267550.CrossRefGoogle ScholarPubMed
Bagan, J, Sarrion, G and Jimenez, Y (2010) Oral cancer: clinical features. Oral Oncology 46, 414417.CrossRefGoogle ScholarPubMed
Chen, CF et al. (2014) Regulation of T cell proliferation by JMJD6 and PDGF-BB during chronic hepatitis B infection. Scientific Reports 4, 6359.CrossRefGoogle ScholarPubMed
Lawrence, P et al. (2016) Pathogenesis and micro-anatomic characterization of a cell-adapted mutant foot-and-mouth disease virus in cattle: Impact of the Jumonji C-domain containing protein 6 (JMJD6) and route of inoculation. Virology 492, 108117.CrossRefGoogle ScholarPubMed
Yanagihara, T et al. (2015) Intronic regulation of Aire expression by Jmjd6 for self-tolerance induction in the thymus. Nature Communications 6, 8820.CrossRefGoogle ScholarPubMed
Walsh, MC, Lee, J and Choi, Y (2015) Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system. Immunological Reviews 266, 7292.CrossRefGoogle ScholarPubMed
Boeckel, JN et al. (2011) Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1. Proceedings of the National Academy of Sciences of the United States of America 108, 32763281.CrossRefGoogle ScholarPubMed
Wu, FT et al. (2010) A systems biology perspective on sVEGFR1: its biological function, pathogenic role and therapeutic use. Journal of Cellular and Molecular Medicine 14, 528552.Google ScholarPubMed
Maynard, SE et al. (2003) Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. Journal of Clinical Investigation 111, 649658.CrossRefGoogle ScholarPubMed
Xia, X et al. (2009) Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis. Proceedings of the National Academy of Sciences of the United States of America 106, 42604265.CrossRefGoogle ScholarPubMed
Alahari, S et al. (2018) Compromised JMJD6 histone demethylase activity affects VHL gene repression in preeclampsia. Journal of Clinical Endocrinology and Metabolism 103, 15451557.CrossRefGoogle ScholarPubMed
Palmer, KR et al. (2016) Jumonji domain containing protein 6 Is decreased in human preeclamptic placentas and regulates sFLT-1 splice variant production. Biology of Reproduction 94, 59.CrossRefGoogle ScholarPubMed
Demir, R, Seval, Y and Huppertz, B (2007) Vasculogenesis and angiogenesis in the early human placenta. Acta Histochemica 109, 257265.CrossRefGoogle ScholarPubMed
Azevedo Portilho, N and Pelajo-Machado, M (2018) Mechanism of hematopoiesis and vasculogenesis in mouse placenta. Placenta 69, 140145.CrossRefGoogle ScholarPubMed
Knofler, M et al. (2019) Human placenta and trophoblast development: key molecular mechanisms and model systems. Cellular and Molecular Life Sciences 76, 34793496.CrossRefGoogle ScholarPubMed
Moser, G et al. (2018) Human trophoblast invasion: new and unexpected routes and functions. Histochemistry and Cell Biology 150, 361370.CrossRefGoogle ScholarPubMed
Maltepe, E and Fisher, SJ (2015) Placenta: the forgotten organ. Annual Review of Cell and Developmental Biology 31, 523552.CrossRefGoogle ScholarPubMed
Pedersen, MT and Helin, K (2010) Histone demethylases in development and disease. Trends in Cell Biology 20, 662671.CrossRefGoogle ScholarPubMed
Fadok, VA et al. (2000) A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405, 8590.CrossRefGoogle ScholarPubMed
Fadok, VA et al. (2001) Loss of phospholipid asymmetry and surface exposure of phosphatidylserine is required for phagocytosis of apoptotic cells by macrophages and fibroblasts. Journal of Biological Chemistry 276, 10711077.CrossRefGoogle ScholarPubMed
Cikala, M et al. (2004) The phosphatidylserine receptor from Hydra is a nuclear protein with potential Fe(II) dependent oxygenase activity. BMC Cell Biology 5, 26.CrossRefGoogle ScholarPubMed
Bose, J et al. (2004) The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal. Journal of Biology 3, 15.CrossRefGoogle ScholarPubMed
Kunisaki, Y et al. (2004) Defective fetal liver erythropoiesis and T lymphopoiesis in mice lacking the phosphatidylserine receptor. Blood 103, 33623364.CrossRefGoogle Scholar
Chang, B et al. (2007) JMJD6 is a histone arginine demethylase. Science (New York, N.Y.) 318, 444447.CrossRefGoogle ScholarPubMed
Webby, CJ et al. (2009) Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing. Science (New York, N.Y.) 325, 9093.CrossRefGoogle ScholarPubMed
Liu, W et al. (2013) Brd4 and JMJD6-associated anti-pause enhancers in regulation of transcriptional pause release. Cell 155, 15811595.CrossRefGoogle ScholarPubMed
Lee, YF et al. (2012) JMJD6 is a driver of cellular proliferation and motility and a marker of poor prognosis in breast cancer. Breast Cancer Research: BCR 14, R85.CrossRefGoogle Scholar
Cui, P et al. (2004) Nuclear localization of the phosphatidylserine receptor protein via multiple nuclear localization signals. Experimental Cell Research 293, 154163.CrossRefGoogle ScholarPubMed
Hahn, P et al. (2008) Genomic structure and expression of Jmjd6 and evolutionary analysis in the context of related JmjC domain containing proteins. BMC Genomics 9, 293.CrossRefGoogle ScholarPubMed
Clissold, PM and Ponting, CP (2001) JmjC: cupin metalloenzyme-like domains in jumonji, hairless and phospholipase A2beta. Trends in Biochemical Sciences 26, 79.CrossRefGoogle ScholarPubMed
Bottger, A et al. (2015) The oxygenase Jmjd6 – a case study in conflicting assignments. Biochemical Journal 468, 191202.CrossRefGoogle ScholarPubMed
Aik, W et al. (2012) Role of the jelly-roll fold in substrate binding by 2-oxoglutarate oxygenases. Current Opinion in Structural Biology 22, 691700.CrossRefGoogle ScholarPubMed
Mantri, M et al. (2010) Crystal structure of the 2-oxoglutarate- and Fe(II)-dependent lysyl hydroxylase JMJD6. Journal of Molecular Biology 401, 211222.CrossRefGoogle ScholarPubMed
Hong, X et al. (2010) Interaction of JMJD6 with single-stranded RNA. Proceedings of the National Academy of Sciences of the United States of America 107, 1456814572.CrossRefGoogle ScholarPubMed
Vangimalla, SS et al. (2017) Bifunctional enzyme JMJD6 contributes to multiple disease pathogenesis: new twist on the old story. Biomolecules 7, 41.CrossRefGoogle ScholarPubMed
Kwok, J et al. (2017) Jmjd6, a JmjC dioxygenase with many interaction partners and pleiotropic functions. Frontiers in Genetics 8, 32.CrossRefGoogle ScholarPubMed
Clifton, IJ et al. (2006) Structural studies on 2-oxoglutarate oxygenases and related double-stranded beta-helix fold proteins. Journal of Inorganic Biochemistry 100, 644669.CrossRefGoogle ScholarPubMed
McDonough, MA et al. (2010) Structural studies on human 2-oxoglutarate dependent oxygenases. Current Opinion in Structural Biology 20, 659672.CrossRefGoogle ScholarPubMed
Huth, JR et al. (1997) The solution structure of an HMG-I(Y)-DNA complex defines a new architectural minor groove binding motif. Natural Structural Biology 4, 657665.CrossRefGoogle ScholarPubMed
Wolf, A et al. (2013) The polyserine domain of the lysyl-5 hydroxylase Jmjd6 mediates subnuclear localization. Biochemical Journal 453, 357370.CrossRefGoogle ScholarPubMed
Miotti, S et al. (2017) Antibody-mediated blockade of JMJD6 interaction with collagen I exerts antifibrotic and antimetastatic activities. FASEB Journal 31, 53565370.CrossRefGoogle ScholarPubMed
Zhou, DX et al. (2017) Inhibition of JMJD6 expression reduces the proliferation, migration and invasion of neuroglioma stem cells. Neoplasma 64, 700708.CrossRefGoogle ScholarPubMed
Zhang, J et al. (2013) High expression of JMJD6 predicts unfavorable survival in lung adenocarcinoma. Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine 34, 23972401.CrossRefGoogle ScholarPubMed
Wang, F et al. (2014) JMJD6 Promotes colon carcinogenesis through negative regulation of p53 by hydroxylation. PLoS Biology 12, e1001819.CrossRefGoogle ScholarPubMed
Wan, J et al. (2019) JMJD6 promotes hepatocellular carcinoma carcinogenesis by targeting CDK4. International Journal of Cancer 144, 24892500.CrossRefGoogle ScholarPubMed
Liu, Y et al. (2019) JMJD6 regulates histone H2A.X phosphorylation and promotes autophagy in triple-negative breast cancer cells via a novel tyrosine kinase activity. Oncogene 38, 980997.CrossRefGoogle Scholar
Yi, J et al. (2017) JMJD6 and U2AF65 co-regulate alternative splicing in both JMJD6 enzymatic activity dependent and independent manner. Nucleic Acids Research 45, 35033518.CrossRefGoogle ScholarPubMed
Olsson, AK et al. (2006) VEGF receptor signalling – in control of vascular function. Nature Reviews Molecular Cell Biology 7, 359371.CrossRefGoogle ScholarPubMed
Tsukada, Y et al. (2006) Histone demethylation by a family of JmjC domain-containing proteins. Nature 439, 811816.CrossRefGoogle ScholarPubMed
Hewitson, KS et al. (2002) Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. Journal of Biological Chemistry 277, 2635126355.CrossRefGoogle Scholar
Lando, D et al. (2002) FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes & Development 16, 14661471.CrossRefGoogle ScholarPubMed
Alahari, S, Post, M and Caniggia, I (2015) Jumonji domain containing protein 6: a novel oxygen sensor in the human placenta. Endocrinology 156, 30123025.CrossRefGoogle ScholarPubMed
Pollard, PJ et al. (2008) Regulation of Jumonji-domain-containing histone demethylases by hypoxia-inducible factor (HIF)-1alpha. Biochemical Journal 416, 387394.CrossRefGoogle ScholarPubMed
Wellmann, S et al. (2008) Hypoxia upregulates the histone demethylase JMJD1A via HIF-1. Biochemical and Biophysical Research Communications 372, 892897.CrossRefGoogle ScholarPubMed
Sar, A et al. (2009) Identification and characterization of demethylase JMJD1A as a gene upregulated in the human cellular response to hypoxia. Cell and Tissue Research 337, 223234.CrossRefGoogle ScholarPubMed
Beyer, S et al. (2008) The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF. Journal of Biological Chemistry 283, 3654236552.CrossRefGoogle ScholarPubMed
Krieg, AJ et al. (2010) Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth. Molecular and Cellular Biology 30, 344353.CrossRefGoogle ScholarPubMed
Farrell, A et al. (2019) Faulty oxygen sensing disrupts angiomotin function in trophoblast cell migration and predisposes to preeclampsia. JCI Insight 4, e127009.CrossRefGoogle ScholarPubMed
WHO (2005) In: World Health Report: Making Every Mother and Child Count. World Health Organization.Google Scholar
Nevo, O et al. (2006) Increased expression of sFlt-1 in in vivo and in vitro models of human placental hypoxia is mediated by HIF-1. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 291, R1085R1093.CrossRefGoogle ScholarPubMed
Eddy, AC et al. (2020) Differential regulation of sFlt-1 splicing by U2AF65 and JMJD6 in placental-derived and endothelial cells. Bioscience Reports 40, BSR20193252.CrossRefGoogle ScholarPubMed
Alahari, S et al. (2021) JMJD6 dysfunction due to iron deficiency in preeclampsia disrupts fibronectin homeostasis resulting in diminished trophoblast migration. Frontiers in Cell and Developmental Biology 9, 652607.CrossRefGoogle ScholarPubMed