The role of chromatin-modifying enzymes and histone modifications in the modulation of p16 gene in fumonisin B1-induced toxicity in human kidney cells
Fumonisin B 1 (FB 1 ) poses a risk to animal and human health. Although the effects of FB 1 on sphingolipid metabolism are well documented, there are limited studies covering the epigenetic modifications and early molecular alterations associated with carcinogenesis pathways caused by FB 1 nephrotox...
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| Veröffentlicht in: | Mycotoxin research 2023-08, Vol.39 (3), p.271-283 |
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| creator | Karaman, Ecem Fatma Abudayyak, Mahmoud Ozden, Sibel |
| description | Fumonisin B
1
(FB
1
) poses a risk to animal and human health. Although the effects of FB
1
on sphingolipid metabolism are well documented, there are limited studies covering the epigenetic modifications and early molecular alterations associated with carcinogenesis pathways caused by FB
1
nephrotoxicity. The present study investigates the effects of FB
1
on global DNA methylation, chromatin-modifying enzymes, and histone modification levels of the
p16
gene in human kidney cells (HK-2) after 24 h exposure. An increase (2.23-fold) in the levels of 5-methylcytosine (5-mC) at 100 µmol/L was observed, a change independent from the decrease in gene expression levels of
DNA methyltransferase 1
(
DNMT1
) at 50 and 100 µmol/L; however,
DNMT3a
and
DNMT3b
were significantly upregulated at 100 µmol/L of FB
1
. Dose-dependent downregulation of chromatin-modifying genes was observed after FB
1
exposure. In addition, chromatin immunoprecipitation results showed that 10 µmol/L of FB
1
induced a significant decrease in H3K9ac, H3K9me3 and H3K27me3 modifications of
p16
, while 100 µmol/L of FB
1
caused a significant increase in H3K27me3 levels of
p16
. Taken together, the results suggest that epigenetic mechanisms might play a role in FB
1
carcinogenesis through DNA methylation, and histone and chromatin modifications. |
| doi_str_mv | 10.1007/s12550-023-00494-2 |
| format | Article |
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1
(FB
1
) poses a risk to animal and human health. Although the effects of FB
1
on sphingolipid metabolism are well documented, there are limited studies covering the epigenetic modifications and early molecular alterations associated with carcinogenesis pathways caused by FB
1
nephrotoxicity. The present study investigates the effects of FB
1
on global DNA methylation, chromatin-modifying enzymes, and histone modification levels of the
p16
gene in human kidney cells (HK-2) after 24 h exposure. An increase (2.23-fold) in the levels of 5-methylcytosine (5-mC) at 100 µmol/L was observed, a change independent from the decrease in gene expression levels of
DNA methyltransferase 1
(
DNMT1
) at 50 and 100 µmol/L; however,
DNMT3a
and
DNMT3b
were significantly upregulated at 100 µmol/L of FB
1
. Dose-dependent downregulation of chromatin-modifying genes was observed after FB
1
exposure. In addition, chromatin immunoprecipitation results showed that 10 µmol/L of FB
1
induced a significant decrease in H3K9ac, H3K9me3 and H3K27me3 modifications of
p16
, while 100 µmol/L of FB
1
caused a significant increase in H3K27me3 levels of
p16
. Taken together, the results suggest that epigenetic mechanisms might play a role in FB
1
carcinogenesis through DNA methylation, and histone and chromatin modifications.</description><identifier>ISSN: 0178-7888</identifier><identifier>EISSN: 1867-1632</identifier><identifier>DOI: 10.1007/s12550-023-00494-2</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Biomedical and Life Sciences ; Carcinogenesis ; Carcinogens ; Cells ; Chemistry/Food Science ; Chromatin ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA methyltransferase ; DNMT1 protein ; Enzymes ; Epigenetics ; Fumonisin B1 ; Gene expression ; Health risks ; Histones ; Immunoprecipitation ; Kidneys ; Life Sciences ; Lipid metabolism ; Medical Microbiology ; Medicine/Public Health ; Methylation ; Microbiology ; Original Article ; p16 Protein ; Toxicity ; Toxins</subject><ispartof>Mycotoxin research, 2023-08, Vol.39 (3), p.271-283</ispartof><rights>The Author(s) under exclusive licence to Society for Mycotoxin (Research Gesellschaft für Mykotoxinforschung e.V.) and Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c352t-17e0dbc78e719a56586b28d6e07049aada6197f15a8767887f72d77f1c1596683</citedby><cites>FETCH-LOGICAL-c352t-17e0dbc78e719a56586b28d6e07049aada6197f15a8767887f72d77f1c1596683</cites><orcidid>0000-0002-1504-4546 ; 0000-0003-2286-4777 ; 0000-0002-1662-2504</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12550-023-00494-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12550-023-00494-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids></links><search><creatorcontrib>Karaman, Ecem Fatma</creatorcontrib><creatorcontrib>Abudayyak, Mahmoud</creatorcontrib><creatorcontrib>Ozden, Sibel</creatorcontrib><title>The role of chromatin-modifying enzymes and histone modifications in the modulation of p16 gene in fumonisin B1-induced toxicity in human kidney cells</title><title>Mycotoxin research</title><addtitle>Mycotoxin Res</addtitle><description>Fumonisin B
1
(FB
1
) poses a risk to animal and human health. Although the effects of FB
1
on sphingolipid metabolism are well documented, there are limited studies covering the epigenetic modifications and early molecular alterations associated with carcinogenesis pathways caused by FB
1
nephrotoxicity. The present study investigates the effects of FB
1
on global DNA methylation, chromatin-modifying enzymes, and histone modification levels of the
p16
gene in human kidney cells (HK-2) after 24 h exposure. An increase (2.23-fold) in the levels of 5-methylcytosine (5-mC) at 100 µmol/L was observed, a change independent from the decrease in gene expression levels of
DNA methyltransferase 1
(
DNMT1
) at 50 and 100 µmol/L; however,
DNMT3a
and
DNMT3b
were significantly upregulated at 100 µmol/L of FB
1
. Dose-dependent downregulation of chromatin-modifying genes was observed after FB
1
exposure. In addition, chromatin immunoprecipitation results showed that 10 µmol/L of FB
1
induced a significant decrease in H3K9ac, H3K9me3 and H3K27me3 modifications of
p16
, while 100 µmol/L of FB
1
caused a significant increase in H3K27me3 levels of
p16
. Taken together, the results suggest that epigenetic mechanisms might play a role in FB
1
carcinogenesis through DNA methylation, and histone and chromatin modifications.</description><subject>Biomedical and Life Sciences</subject><subject>Carcinogenesis</subject><subject>Carcinogens</subject><subject>Cells</subject><subject>Chemistry/Food Science</subject><subject>Chromatin</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA methyltransferase</subject><subject>DNMT1 protein</subject><subject>Enzymes</subject><subject>Epigenetics</subject><subject>Fumonisin B1</subject><subject>Gene expression</subject><subject>Health risks</subject><subject>Histones</subject><subject>Immunoprecipitation</subject><subject>Kidneys</subject><subject>Life Sciences</subject><subject>Lipid metabolism</subject><subject>Medical Microbiology</subject><subject>Medicine/Public Health</subject><subject>Methylation</subject><subject>Microbiology</subject><subject>Original Article</subject><subject>p16 Protein</subject><subject>Toxicity</subject><subject>Toxins</subject><issn>0178-7888</issn><issn>1867-1632</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kcGOFCEURYnRxHb0B1yRuHGDAlXw6KVOHDWZxM24Jgy86mKsghaqEssP8Xulu01MXLiC3HfuzYNLyEvB3wjO4W0VUinOuOwY5_2-Z_IR2QmjgQndycdkxwUYBsaYp-RZrQ-c667XZkd-3Y1IS56Q5oH6seTZLTGxOYc4bDEdKKaf24yVuhToGOuSE9LzNPpG5lRpTHQZz-I6naVT1FFoesDGtumwzjnF2m7vBYsprB4DXfKP6OOynYBxnV2i32JIuFGP01SfkyeDmyq--HNeka83H-6uP7HbLx8_X7-7Zb5TcmECkId7DwZB7J3Syuh7aYJGDu0XnAtOiz0MQjkDur0eBpABmuCF2mttuivy-pJ7LPn7inWxc6ynDVzCvFYrjQSpDIBu6Kt_0Ie8ltS2a1Tfg9K95I2SF8qXXGvBwR5LnF3ZrOD2VJW9VGVbVfZclZXN1F1MtcHpgOVv9H9cvwHXjper</recordid><startdate>20230801</startdate><enddate>20230801</enddate><creator>Karaman, Ecem Fatma</creator><creator>Abudayyak, Mahmoud</creator><creator>Ozden, Sibel</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7T7</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1504-4546</orcidid><orcidid>https://orcid.org/0000-0003-2286-4777</orcidid><orcidid>https://orcid.org/0000-0002-1662-2504</orcidid></search><sort><creationdate>20230801</creationdate><title>The role of chromatin-modifying enzymes and histone modifications in the modulation of p16 gene in fumonisin B1-induced toxicity in human kidney cells</title><author>Karaman, Ecem Fatma ; Abudayyak, Mahmoud ; Ozden, Sibel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c352t-17e0dbc78e719a56586b28d6e07049aada6197f15a8767887f72d77f1c1596683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Biomedical and Life Sciences</topic><topic>Carcinogenesis</topic><topic>Carcinogens</topic><topic>Cells</topic><topic>Chemistry/Food Science</topic><topic>Chromatin</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>DNA methyltransferase</topic><topic>DNMT1 protein</topic><topic>Enzymes</topic><topic>Epigenetics</topic><topic>Fumonisin B1</topic><topic>Gene expression</topic><topic>Health risks</topic><topic>Histones</topic><topic>Immunoprecipitation</topic><topic>Kidneys</topic><topic>Life Sciences</topic><topic>Lipid metabolism</topic><topic>Medical Microbiology</topic><topic>Medicine/Public Health</topic><topic>Methylation</topic><topic>Microbiology</topic><topic>Original Article</topic><topic>p16 Protein</topic><topic>Toxicity</topic><topic>Toxins</topic><toplevel>online_resources</toplevel><creatorcontrib>Karaman, Ecem Fatma</creatorcontrib><creatorcontrib>Abudayyak, Mahmoud</creatorcontrib><creatorcontrib>Ozden, Sibel</creatorcontrib><collection>CrossRef</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Mycotoxin research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Karaman, Ecem Fatma</au><au>Abudayyak, Mahmoud</au><au>Ozden, Sibel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of chromatin-modifying enzymes and histone modifications in the modulation of p16 gene in fumonisin B1-induced toxicity in human kidney cells</atitle><jtitle>Mycotoxin research</jtitle><stitle>Mycotoxin Res</stitle><date>2023-08-01</date><risdate>2023</risdate><volume>39</volume><issue>3</issue><spage>271</spage><epage>283</epage><pages>271-283</pages><issn>0178-7888</issn><eissn>1867-1632</eissn><abstract>Fumonisin B
1
(FB
1
) poses a risk to animal and human health. Although the effects of FB
1
on sphingolipid metabolism are well documented, there are limited studies covering the epigenetic modifications and early molecular alterations associated with carcinogenesis pathways caused by FB
1
nephrotoxicity. The present study investigates the effects of FB
1
on global DNA methylation, chromatin-modifying enzymes, and histone modification levels of the
p16
gene in human kidney cells (HK-2) after 24 h exposure. An increase (2.23-fold) in the levels of 5-methylcytosine (5-mC) at 100 µmol/L was observed, a change independent from the decrease in gene expression levels of
DNA methyltransferase 1
(
DNMT1
) at 50 and 100 µmol/L; however,
DNMT3a
and
DNMT3b
were significantly upregulated at 100 µmol/L of FB
1
. Dose-dependent downregulation of chromatin-modifying genes was observed after FB
1
exposure. In addition, chromatin immunoprecipitation results showed that 10 µmol/L of FB
1
induced a significant decrease in H3K9ac, H3K9me3 and H3K27me3 modifications of
p16
, while 100 µmol/L of FB
1
caused a significant increase in H3K27me3 levels of
p16
. Taken together, the results suggest that epigenetic mechanisms might play a role in FB
1
carcinogenesis through DNA methylation, and histone and chromatin modifications.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><doi>10.1007/s12550-023-00494-2</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-1504-4546</orcidid><orcidid>https://orcid.org/0000-0003-2286-4777</orcidid><orcidid>https://orcid.org/0000-0002-1662-2504</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0178-7888 |
| ispartof | Mycotoxin research, 2023-08, Vol.39 (3), p.271-283 |
| issn | 0178-7888 1867-1632 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2827258776 |
| source | SpringerLink Journals - AutoHoldings |
| subjects | Biomedical and Life Sciences Carcinogenesis Carcinogens Cells Chemistry/Food Science Chromatin Deoxyribonucleic acid DNA DNA methylation DNA methyltransferase DNMT1 protein Enzymes Epigenetics Fumonisin B1 Gene expression Health risks Histones Immunoprecipitation Kidneys Life Sciences Lipid metabolism Medical Microbiology Medicine/Public Health Methylation Microbiology Original Article p16 Protein Toxicity Toxins |
| title | The role of chromatin-modifying enzymes and histone modifications in the modulation of p16 gene in fumonisin B1-induced toxicity in human kidney cells |
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