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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Veröffentlicht in:Journal of cellular and molecular medicine 2011-07, Vol.15 (7), p.1603-1614
Hauptverfasser: Bhandari, Dilli Ram, Seo, Kwang‐Won, Jung, Ji‐Won, Kim, Hyung‐Sik, Yang, Se‐Ran, Kang, Kyung‐Sun
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container_title Journal of cellular and molecular medicine
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creator Bhandari, Dilli Ram
Seo, Kwang‐Won
Jung, Ji‐Won
Kim, Hyung‐Sik
Yang, Se‐Ran
Kang, Kyung‐Sun
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. 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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. 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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.</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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