The regulatory role of c‐MYC on HDAC2 and PcG expression in human multipotent stem cells
Myelocytomatosis oncogene (c‐MYC) is a well‐known nuclear oncoprotein having multiple functions in cell proliferation, apoptosis and cellular transformation. Chromosomal modification is also important to the differentiation and growth of stem cells. Histone deacethylase (HDAC) and polycomb group (Pc...
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description | Myelocytomatosis oncogene (c‐MYC) is a well‐known nuclear oncoprotein having multiple functions in cell proliferation, apoptosis and cellular transformation. Chromosomal modification is also important to the differentiation and growth of stem cells. Histone deacethylase (HDAC) and polycomb group (PcG) family genes are well‐known chromosomal modification genes. The aim of this study was to elucidate the role of c‐MYC in the expression of chromosomal modification via the HDAC family genes in human mesenchymal stem cells (hMSCs). To achieve this goal, c‐MYC expression was modified by gene knockdown and overexpression via lentivirus vector. Using the modified c‐MYC expression, our study was focused on cell proliferation, differentiation and cell cycle. Furthermore, the relationship of c‐MYC with HDAC2 and PcG genes was also examined. The cell proliferation and differentiation were checked and shown to be dramatically decreased in c‐MYC knocked‐down human umbilical cord blood‐derived MSCs, whereas they were increased in c‐MYC overexpressing cells. Similarly, RT‐PCR and Western blotting results revealed that HDAC2 expression was decreased in c‐MYC knocked‐down and increased in c‐MYC overexpressing hMSCs. Database indicates presence of c‐MYC binding motif in HDAC2 promoter region, which was confirmed by chromatin immunoprecipitation assay. The influence of c‐MYC and HDAC2 on PcG expression was confirmed. This might indicate the regulatory role of c‐MYC over HDAC2 and PcG genes. c‐MYCs’ regulatory role over HDAC2 was also confirmed in human adipose tissue‐derived MSCs and bone‐marrow derived MSCs. From this finding, it can be concluded that c‐MYC plays a vital role in cell proliferation and differentiation via chromosomal modification. |
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Chromosomal modification is also important to the differentiation and growth of stem cells. Histone deacethylase (HDAC) and polycomb group (PcG) family genes are well‐known chromosomal modification genes. The aim of this study was to elucidate the role of c‐MYC in the expression of chromosomal modification via the HDAC family genes in human mesenchymal stem cells (hMSCs). To achieve this goal, c‐MYC expression was modified by gene knockdown and overexpression via lentivirus vector. Using the modified c‐MYC expression, our study was focused on cell proliferation, differentiation and cell cycle. Furthermore, the relationship of c‐MYC with HDAC2 and PcG genes was also examined. The cell proliferation and differentiation were checked and shown to be dramatically decreased in c‐MYC knocked‐down human umbilical cord blood‐derived MSCs, whereas they were increased in c‐MYC overexpressing cells. Similarly, RT‐PCR and Western blotting results revealed that HDAC2 expression was decreased in c‐MYC knocked‐down and increased in c‐MYC overexpressing hMSCs. Database indicates presence of c‐MYC binding motif in HDAC2 promoter region, which was confirmed by chromatin immunoprecipitation assay. The influence of c‐MYC and HDAC2 on PcG expression was confirmed. This might indicate the regulatory role of c‐MYC over HDAC2 and PcG genes. c‐MYCs’ regulatory role over HDAC2 was also confirmed in human adipose tissue‐derived MSCs and bone‐marrow derived MSCs. From this finding, it can be concluded that c‐MYC plays a vital role in cell proliferation and differentiation via chromosomal modification.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/j.1582-4934.2010.01144.x</identifier><identifier>PMID: 20716118</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adipose tissue ; Apoptosis ; Body fat ; c-Myc protein ; Cancer ; Cell culture ; Cell Cycle ; Cell Differentiation ; Cell growth ; Cell Proliferation ; Chromatin ; Cord blood ; c‐MYC ; differentiation ; Gene Expression Regulation ; Gene Knockdown Techniques ; Genes ; HDAC2 ; HDAC2 protein ; Histone deacetylase ; Histone Deacetylase 2 - genetics ; Histone Deacetylase 2 - metabolism ; Histones ; hMSCs ; Humans ; Immunoprecipitation ; Mesenchymal stem cells ; Multipotent Stem Cells - physiology ; Myc protein ; PcG ; Polycomb group proteins ; proliferation ; Promoter Regions, Genetic ; Proteins ; Proto-Oncogene Proteins c-myc - genetics ; Proto-Oncogene Proteins c-myc - metabolism ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; Review boards ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; stem cell ; Stem cells ; Transcription factors ; Umbilical cord ; Western blotting ; Yeast</subject><ispartof>Journal of cellular and molecular medicine, 2011-07, Vol.15 (7), p.1603-1614</ispartof><rights>2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd</rights><rights>2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.</rights><rights>2011. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5024-9c6f6725365862274da8e4fe83ffa93a6acc049e3eda8370789760f50bbb72bb3</citedby><cites>FETCH-LOGICAL-c5024-9c6f6725365862274da8e4fe83ffa93a6acc049e3eda8370789760f50bbb72bb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823204/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823204/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><linktorsrc>$$Uhttps://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1582-4934.2010.01144.x$$EView_record_in_Wiley-Blackwell$$FView_record_in_$$GWiley-Blackwell</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20716118$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bhandari, Dilli Ram</creatorcontrib><creatorcontrib>Seo, Kwang‐Won</creatorcontrib><creatorcontrib>Jung, Ji‐Won</creatorcontrib><creatorcontrib>Kim, Hyung‐Sik</creatorcontrib><creatorcontrib>Yang, Se‐Ran</creatorcontrib><creatorcontrib>Kang, Kyung‐Sun</creatorcontrib><title>The regulatory role of c‐MYC on HDAC2 and PcG expression in human multipotent stem cells</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>Myelocytomatosis oncogene (c‐MYC) is a well‐known nuclear oncoprotein having multiple functions in cell proliferation, apoptosis and cellular transformation. Chromosomal modification is also important to the differentiation and growth of stem cells. Histone deacethylase (HDAC) and polycomb group (PcG) family genes are well‐known chromosomal modification genes. The aim of this study was to elucidate the role of c‐MYC in the expression of chromosomal modification via the HDAC family genes in human mesenchymal stem cells (hMSCs). To achieve this goal, c‐MYC expression was modified by gene knockdown and overexpression via lentivirus vector. Using the modified c‐MYC expression, our study was focused on cell proliferation, differentiation and cell cycle. Furthermore, the relationship of c‐MYC with HDAC2 and PcG genes was also examined. The cell proliferation and differentiation were checked and shown to be dramatically decreased in c‐MYC knocked‐down human umbilical cord blood‐derived MSCs, whereas they were increased in c‐MYC overexpressing cells. Similarly, RT‐PCR and Western blotting results revealed that HDAC2 expression was decreased in c‐MYC knocked‐down and increased in c‐MYC overexpressing hMSCs. Database indicates presence of c‐MYC binding motif in HDAC2 promoter region, which was confirmed by chromatin immunoprecipitation assay. The influence of c‐MYC and HDAC2 on PcG expression was confirmed. This might indicate the regulatory role of c‐MYC over HDAC2 and PcG genes. c‐MYCs’ regulatory role over HDAC2 was also confirmed in human adipose tissue‐derived MSCs and bone‐marrow derived MSCs. From this finding, it can be concluded that c‐MYC plays a vital role in cell proliferation and differentiation via chromosomal modification.</description><subject>Adipose tissue</subject><subject>Apoptosis</subject><subject>Body fat</subject><subject>c-Myc protein</subject><subject>Cancer</subject><subject>Cell culture</subject><subject>Cell Cycle</subject><subject>Cell Differentiation</subject><subject>Cell growth</subject><subject>Cell Proliferation</subject><subject>Chromatin</subject><subject>Cord blood</subject><subject>c‐MYC</subject><subject>differentiation</subject><subject>Gene Expression Regulation</subject><subject>Gene Knockdown Techniques</subject><subject>Genes</subject><subject>HDAC2</subject><subject>HDAC2 protein</subject><subject>Histone deacetylase</subject><subject>Histone Deacetylase 2 - genetics</subject><subject>Histone Deacetylase 2 - metabolism</subject><subject>Histones</subject><subject>hMSCs</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Mesenchymal stem cells</subject><subject>Multipotent Stem Cells - physiology</subject><subject>Myc protein</subject><subject>PcG</subject><subject>Polycomb group proteins</subject><subject>proliferation</subject><subject>Promoter Regions, Genetic</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-myc - genetics</subject><subject>Proto-Oncogene Proteins c-myc - metabolism</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - metabolism</subject><subject>Review boards</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>stem cell</subject><subject>Stem cells</subject><subject>Transcription factors</subject><subject>Umbilical cord</subject><subject>Western blotting</subject><subject>Yeast</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNUc1u1DAYtBCI_sArVJZ64LRb_8V2LkhVCi1VV3AoB7hYjvdLN6sk3toJ7N76CH3GPglOuyyFE774k2e-8YwGIUzJlKZzspzSTLOJyLmYMpJeCaVCTNcv0P4OeLmdqeZ6Dx3EuCSES8rz12iPEUUlpXoffb9eAA5wMzS292GDg28A-wq7h7v72bcC-w5fnJ0WDNtujr-4cwzrVYAY6wTUHV4Mre1wOzR9vfI9dD2OPbTYQdPEN-hVZZsIb7f3Ifr68cN1cTG5-nz-qTi9mriMMDHJnaykYhmXmZaMKTG3GkQFmleVzbmV1jkicuCQAK6I0rmSpMpIWZaKlSU_RO-fdFdD2cLcJRfBNmYV6taGjfG2Nn8jXb0wN_6H4ZpxRkQSeLcVCP52gNibto5jBNuBH6LRKn0rxSPz-B_m0g-hS-kMJyrLk3-iE0s_sVzwMQaodl4oMWN_ZmnGasxYkxn7M4_9mXVaPXqeZbf4u7A_YX_WDWz-W9hcFrPZOPJf8FipwQ</recordid><startdate>201107</startdate><enddate>201107</enddate><creator>Bhandari, Dilli Ram</creator><creator>Seo, Kwang‐Won</creator><creator>Jung, Ji‐Won</creator><creator>Kim, Hyung‐Sik</creator><creator>Yang, Se‐Ran</creator><creator>Kang, Kyung‐Sun</creator><general>Blackwell Publishing Ltd</general><general>John Wiley & Sons, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201107</creationdate><title>The regulatory role of c‐MYC on HDAC2 and PcG expression in human multipotent stem cells</title><author>Bhandari, Dilli Ram ; Seo, Kwang‐Won ; Jung, Ji‐Won ; Kim, Hyung‐Sik ; Yang, Se‐Ran ; Kang, Kyung‐Sun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5024-9c6f6725365862274da8e4fe83ffa93a6acc049e3eda8370789760f50bbb72bb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adipose tissue</topic><topic>Apoptosis</topic><topic>Body fat</topic><topic>c-Myc protein</topic><topic>Cancer</topic><topic>Cell culture</topic><topic>Cell Cycle</topic><topic>Cell Differentiation</topic><topic>Cell growth</topic><topic>Cell Proliferation</topic><topic>Chromatin</topic><topic>Cord blood</topic><topic>c‐MYC</topic><topic>differentiation</topic><topic>Gene Expression Regulation</topic><topic>Gene Knockdown Techniques</topic><topic>Genes</topic><topic>HDAC2</topic><topic>HDAC2 protein</topic><topic>Histone deacetylase</topic><topic>Histone Deacetylase 2 - genetics</topic><topic>Histone Deacetylase 2 - metabolism</topic><topic>Histones</topic><topic>hMSCs</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Mesenchymal stem cells</topic><topic>Multipotent Stem Cells - physiology</topic><topic>Myc protein</topic><topic>PcG</topic><topic>Polycomb group proteins</topic><topic>proliferation</topic><topic>Promoter Regions, Genetic</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-myc - genetics</topic><topic>Proto-Oncogene Proteins c-myc - metabolism</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - metabolism</topic><topic>Review boards</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - metabolism</topic><topic>stem cell</topic><topic>Stem cells</topic><topic>Transcription factors</topic><topic>Umbilical cord</topic><topic>Western blotting</topic><topic>Yeast</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bhandari, Dilli Ram</creatorcontrib><creatorcontrib>Seo, Kwang‐Won</creatorcontrib><creatorcontrib>Jung, Ji‐Won</creatorcontrib><creatorcontrib>Kim, Hyung‐Sik</creatorcontrib><creatorcontrib>Yang, Se‐Ran</creatorcontrib><creatorcontrib>Kang, Kyung‐Sun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Bhandari, Dilli Ram</au><au>Seo, Kwang‐Won</au><au>Jung, Ji‐Won</au><au>Kim, Hyung‐Sik</au><au>Yang, Se‐Ran</au><au>Kang, Kyung‐Sun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The regulatory role of c‐MYC on HDAC2 and PcG expression in human multipotent stem cells</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2011-07</date><risdate>2011</risdate><volume>15</volume><issue>7</issue><spage>1603</spage><epage>1614</epage><pages>1603-1614</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>Myelocytomatosis oncogene (c‐MYC) is a well‐known nuclear oncoprotein having multiple functions in cell proliferation, apoptosis and cellular transformation. Chromosomal modification is also important to the differentiation and growth of stem cells. Histone deacethylase (HDAC) and polycomb group (PcG) family genes are well‐known chromosomal modification genes. The aim of this study was to elucidate the role of c‐MYC in the expression of chromosomal modification via the HDAC family genes in human mesenchymal stem cells (hMSCs). To achieve this goal, c‐MYC expression was modified by gene knockdown and overexpression via lentivirus vector. Using the modified c‐MYC expression, our study was focused on cell proliferation, differentiation and cell cycle. Furthermore, the relationship of c‐MYC with HDAC2 and PcG genes was also examined. The cell proliferation and differentiation were checked and shown to be dramatically decreased in c‐MYC knocked‐down human umbilical cord blood‐derived MSCs, whereas they were increased in c‐MYC overexpressing cells. Similarly, RT‐PCR and Western blotting results revealed that HDAC2 expression was decreased in c‐MYC knocked‐down and increased in c‐MYC overexpressing hMSCs. Database indicates presence of c‐MYC binding motif in HDAC2 promoter region, which was confirmed by chromatin immunoprecipitation assay. The influence of c‐MYC and HDAC2 on PcG expression was confirmed. This might indicate the regulatory role of c‐MYC over HDAC2 and PcG genes. c‐MYCs’ regulatory role over HDAC2 was also confirmed in human adipose tissue‐derived MSCs and bone‐marrow derived MSCs. From this finding, it can be concluded that c‐MYC plays a vital role in cell proliferation and differentiation via chromosomal modification.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>20716118</pmid><doi>10.1111/j.1582-4934.2010.01144.x</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adipose tissue Apoptosis Body fat c-Myc protein Cancer Cell culture Cell Cycle Cell Differentiation Cell growth Cell Proliferation Chromatin Cord blood c‐MYC differentiation Gene Expression Regulation Gene Knockdown Techniques Genes HDAC2 HDAC2 protein Histone deacetylase Histone Deacetylase 2 - genetics Histone Deacetylase 2 - metabolism Histones hMSCs Humans Immunoprecipitation Mesenchymal stem cells Multipotent Stem Cells - physiology Myc protein PcG Polycomb group proteins proliferation Promoter Regions, Genetic Proteins Proto-Oncogene Proteins c-myc - genetics Proto-Oncogene Proteins c-myc - metabolism Repressor Proteins - genetics Repressor Proteins - metabolism Review boards RNA, Small Interfering - genetics RNA, Small Interfering - metabolism stem cell Stem cells Transcription factors Umbilical cord Western blotting Yeast |
title | The regulatory role of c‐MYC on HDAC2 and PcG expression in human multipotent stem cells |
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