DNA topoisomerase II is involved in regulation of cyst wall protein genes and differentiation in Giardia lamblia.
The protozoan Giardia lamblia differentiates into infectious cysts within the human intestinal tract for disease transmission. Expression of the cyst wall protein (cwp) genes increases with similar kinetics during encystation. However, little is known how their gene regulation shares common mechanis...
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ftdoajarticles:oai:doaj.org/article:dc89838426b646bea82c714a721a34d4 2023-05-15T15:13:20+02:00 DNA topoisomerase II is involved in regulation of cyst wall protein genes and differentiation in Giardia lamblia. Bo-Chi Lin Li-Hsin Su Shih-Che Weng Yu-Jiao Pan Nei-Li Chan Tsai-Kun Li Hsin-Chih Wang Chin-Hung Sun 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002218 https://doaj.org/article/dc89838426b646bea82c714a721a34d4 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3656124?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002218 https://doaj.org/article/dc89838426b646bea82c714a721a34d4 PLoS Neglected Tropical Diseases, Vol 7, Iss 5, p e2218 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002218 2022-12-31T01:09:27Z The protozoan Giardia lamblia differentiates into infectious cysts within the human intestinal tract for disease transmission. Expression of the cyst wall protein (cwp) genes increases with similar kinetics during encystation. However, little is known how their gene regulation shares common mechanisms. DNA topoisomerases maintain normal topology of genomic DNA. They are necessary for cell proliferation and tissue development as they are involved in transcription, DNA replication, and chromosome condensation. A putative topoisomerase II (topo II) gene has been identified in the G. lamblia genome. We asked whether Topo II could regulate Giardia encystation. We found that Topo II was present in cell nuclei and its gene was up-regulated during encystation. Topo II has typical ATPase and DNA cleavage activity of type II topoisomerases. Mutation analysis revealed that the catalytic important Tyr residue and cleavage domain are important for Topo II function. We used etoposide-mediated topoisomerase immunoprecipitation assays to confirm the binding of Topo II to the cwp promoters in vivo. Interestingly, Topo II overexpression increased the levels of cwp gene expression and cyst formation. Microarray analysis identified up-regulation of cwp and specific vsp genes by Topo II. We also found that the type II topoisomerase inhibitor etoposide has growth inhibition effect on Giardia. Addition of etoposide significantly decreased the levels of cwp gene expression and cyst formation. Our results suggest that Topo II has been functionally conserved during evolution and that Topo II plays important roles in induction of the cwp genes, which is key to Giardia differentiation into cysts. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 5 e2218 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Bo-Chi Lin Li-Hsin Su Shih-Che Weng Yu-Jiao Pan Nei-Li Chan Tsai-Kun Li Hsin-Chih Wang Chin-Hung Sun DNA topoisomerase II is involved in regulation of cyst wall protein genes and differentiation in Giardia lamblia. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
The protozoan Giardia lamblia differentiates into infectious cysts within the human intestinal tract for disease transmission. Expression of the cyst wall protein (cwp) genes increases with similar kinetics during encystation. However, little is known how their gene regulation shares common mechanisms. DNA topoisomerases maintain normal topology of genomic DNA. They are necessary for cell proliferation and tissue development as they are involved in transcription, DNA replication, and chromosome condensation. A putative topoisomerase II (topo II) gene has been identified in the G. lamblia genome. We asked whether Topo II could regulate Giardia encystation. We found that Topo II was present in cell nuclei and its gene was up-regulated during encystation. Topo II has typical ATPase and DNA cleavage activity of type II topoisomerases. Mutation analysis revealed that the catalytic important Tyr residue and cleavage domain are important for Topo II function. We used etoposide-mediated topoisomerase immunoprecipitation assays to confirm the binding of Topo II to the cwp promoters in vivo. Interestingly, Topo II overexpression increased the levels of cwp gene expression and cyst formation. Microarray analysis identified up-regulation of cwp and specific vsp genes by Topo II. We also found that the type II topoisomerase inhibitor etoposide has growth inhibition effect on Giardia. Addition of etoposide significantly decreased the levels of cwp gene expression and cyst formation. Our results suggest that Topo II has been functionally conserved during evolution and that Topo II plays important roles in induction of the cwp genes, which is key to Giardia differentiation into cysts. |
format |
Article in Journal/Newspaper |
author |
Bo-Chi Lin Li-Hsin Su Shih-Che Weng Yu-Jiao Pan Nei-Li Chan Tsai-Kun Li Hsin-Chih Wang Chin-Hung Sun |
author_facet |
Bo-Chi Lin Li-Hsin Su Shih-Che Weng Yu-Jiao Pan Nei-Li Chan Tsai-Kun Li Hsin-Chih Wang Chin-Hung Sun |
author_sort |
Bo-Chi Lin |
title |
DNA topoisomerase II is involved in regulation of cyst wall protein genes and differentiation in Giardia lamblia. |
title_short |
DNA topoisomerase II is involved in regulation of cyst wall protein genes and differentiation in Giardia lamblia. |
title_full |
DNA topoisomerase II is involved in regulation of cyst wall protein genes and differentiation in Giardia lamblia. |
title_fullStr |
DNA topoisomerase II is involved in regulation of cyst wall protein genes and differentiation in Giardia lamblia. |
title_full_unstemmed |
DNA topoisomerase II is involved in regulation of cyst wall protein genes and differentiation in Giardia lamblia. |
title_sort |
dna topoisomerase ii is involved in regulation of cyst wall protein genes and differentiation in giardia lamblia. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002218 https://doaj.org/article/dc89838426b646bea82c714a721a34d4 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 5, p e2218 (2013) |
op_relation |
http://europepmc.org/articles/PMC3656124?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002218 https://doaj.org/article/dc89838426b646bea82c714a721a34d4 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002218 |
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PLoS Neglected Tropical Diseases |
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7 |
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5 |
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e2218 |
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1766343893384691712 |