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FOXO3a Potentiates hTERT Gene Expression by Activating c-MYC and Extends the Replicative Life-Span of Human Fibroblast

Shuntaro Yamashita, Kaori Ogawa, Takahiro Ikei, Tsukasa Fujiki, Yoshinori Katakura, Frédérique Magdinier
2014 PLoS ONE  
In addition, we found that FOXO3a binds to the novel binding element in the c-MYC promoter, and this interaction activates the transcription of the c-MYC gene.  ...  The resulting increase in c-MYC leads to higher levels of c-MYC recruited to the hTERT promoter and, in turn, activates hTERT gene expression.  ...  Figure 4 . 4 Identification of c-MYC promoter elements required for FOXO3a-mediated activation. A, Schematic representation of the human c-MYC promoter (c-MYCpWT) and its derivatives.  ... 
doi:10.1371/journal.pone.0101864 pmid:25000517 pmcid:PMC4085005 fatcat:cqnnzn3o4varphfrxi6ghxebde

Identification of two enhancer elements downstream of the human c-mycgene

Josef Mautner, Stefan Joos, Thomas Werner, Dirk Eick, Georg W. Bornkamm, Axel Polack
1995 Nucleic Acids Research  
Transcription of c-myc in vivo thus requires additional control elements located outside the tested H/ndlll-EcoRI gene fragment.  ...  In order to identify these putative additional control elements, we mapped DNase I hypersensitive sites around the human c-myc gene in nine different tumor cell lines and in primary lymphocytes.  ...  With these experiments we identified two activating elements in the 3' region of the human c-myc gene, colocalizing with HS 6.5 (fragment 29i) and HS 18 and 19 (fragment 281b), respectively.  ... 
doi:10.1093/nar/23.1.72 pmid:7870592 pmcid:PMC306632 fatcat:jyczxf45hjhu5ez3plxju7cfwq

Regulation ofMYCgene expression by aberrant Wnt/β-catenin signaling in colorectal cancer

Sherri Rennoll
2015 World Journal of Biological Chemsitry  
Deregulated expression of the c-MYC proto-oncogene (MYC ) by aberrant Wnt/ β-catenin signaling drives colorectal carcinogenesis.  ...  These mutations lead to inappropriate expression of genes controlled by Wnt responsive DNA elements (WREs).  ...  CONCLUSION Despite the identification of MYC over 30 years ago Recent reports have indicated that active DNA enhancer elements express short, bidirectional RNAs termed enhancer RNAs (eRNAs) [81] [82  ... 
doi:10.4331/wjbc.v6.i4.290 pmid:26629312 pmcid:PMC4657124 fatcat:3gfzz76fvre2bd5xod2morz37y

What retroviruses teach us about the involvement of c-Myc in leukemias and lymphomas

JP Dudley, JA Mertz, L Rajan, M Lozano, DR Broussard
2002 Leukemia  
Studies of the LTR enhancer elements from these retroviruses have revealed the importance of these elements for c-Myc activation in several cell types.  ...  Retroviruses have enhanced our understanding of the role of c-Myc in such tumors.  ...  Acknowledgements This work was supported by Public Health Service Grants CA34780 and CA77760 from the US National Cancer Institute.  ... 
doi:10.1038/sj.leu.2402451 pmid:12040439 fatcat:4wi53horojbr3a5zm323bbhc5y

The c-myc Insulator Element and Matrix Attachment Regions Define the c-myc Chromosomal Domain

W. M. Gombert, S. D. Farris, E. D. Rubio, K. M. Morey-Rosler, W. H. Schubach, A. Krumm
2003 Molecular and Cellular Biology  
By comparing the pattern of histone modifications at the mouse and human c-myc alleles, we identified an evolutionarily conserved boundary at which the c-myc transcription unit is separated from the flanking  ...  This region harbors the c-myc insulator element (MINE), which contains at least two physically separable, functional activities: enhancerblocking activity and barrier activity.  ...  Results from the human c-myc gene are based on two independent experiments using different chromatin preparations.  ... 
doi:10.1128/mcb.23.24.9338-9348.2003 pmid:14645543 pmcid:PMC309672 fatcat:xxaddsogt5dvre53ngcmlmmz6e

Activation of a translocated human c-myc gene by an enhancer in the immunoglobulin heavy-chain locus

Adrian C. Hayday, Stephen D. Gillies, Haruo Saito, Charles Wood, Klas Wiman, William S. Hayward, Susumu Tonegawa
1984 Nature  
In a non-Hodgkin's lymphoma that contains a translocated c-myc gene this enhancer is retained on the 14q + chromosome and occurs within sequences shown to activate previously cryptic promoters of the c-myc  ...  A tissue-specific transcriptional enhancer element that is associated with the human immunoglobulin heavy-chain locus is defined.  ...  The translocation of the c-myc gene in Manca cell DNA just 300 bp downstream of the human J H cluster ( Figure 1) suggested that the high level of c-myc transcription in Manca cells (Figure 2A) might  ... 
doi:10.1038/307334a0 pmid:6420706 fatcat:zcnz4ogjsfhr7l2nhwgrlo2hya

MYC Drives a Subset of High-Risk Pediatric Neuroblastomas and Is Activated through Mechanisms Including Enhancer Hijacking and Focal Enhancer Amplification

Mark W. Zimmerman, Yu Liu, Shuning He, Adam D. Durbin, Brian J. Abraham, John Easton, Ying Shao, Beisi Xu, Shizhen Zhu, Xiaoling Zhang, Zhaodong Li, Nina Weichert-Leahey (+3 others)
2017 Cancer Discovery  
The aberrant regulatory elements associated with oncogenic c-MYC activation include focally amplified distal enhancers and translocation of highly active enhancers from other genes to within topologically  ...  associating domains containing the c-MYC gene locus.  ...  By examining the sequence results, we identified two genomic mechanisms leading to c-MYC activation: i) focal amplifications that increase the copy number of active cis-regulatory enhancer elements downstream  ... 
doi:10.1158/ pmid:29284669 fatcat:m35otsgto5bmlejtv3gmgxu2ei

An E-box element localized in the first intron mediates regulation of the prothymosin alpha gene by c-myc

S Gaubatz, A Meichle, M Eilers
1994 Molecular and Cellular Biology  
We find that regulation by c-myc is mediated by sequences downstream of the transcriptional start site, whereas the promoter is constitutive and not regulated by c-myc.  ...  In RAT1A fibroblasts, expression of the prothymosin alpha gene is under the transcriptional control of the c-myc proto-oncogene.  ...  ACKNOWLEDGMENTS This work was supported by the Bundesministerium fur Forschung und Technologie (grant BCT0381-5) and the Human Frontier Science Program.  ... 
doi:10.1128/mcb.14.6.3853 pmid:8196628 pmcid:PMC358752 fatcat:f2sy3t2clrejjay42c5744ukme

Global epigenomic analysis of KSHV-infected primary effusion lymphoma identifies functional MYC superenhancers and enhancer RNAs

Angela Park, Soohwan Oh, Kyle L. Jung, Un Yung Choi, Hye-Ra Lee, Michael G. Rosenfeld, Jae U. Jung
2020 Proceedings of the National Academy of Sciences of the United States of America  
The eRNA-expressing MYC superenhancers were located downstream of the MYC gene in KSHV-infected PELs and played a key role in MYC expression.  ...  This revealed that a number of critical host genes for KSHV latency, including MYC proto-oncogene, were under the control of superenhancers whose activities were globally repressed upon viral reactivation  ...  This work was partly supported by NIH grants (CA200422, CA251275, CA250052, AI116585, AI140718, AI140705, DE023926, DE027888, DE028521), and the Fletcher Jones Foundation grant (J.U.J.).  ... 
doi:10.1073/pnas.1922216117 pmid:32817485 fatcat:m47w3lp6mbgirhwfmapv6fkw64

HACER: an atlas of human active enhancers to interpret regulatory variants

2018 Nucleic Acids Research  
To address this need, we built HACER (, an atlas of Human ACtive Enhancers to interpret Regulatory variants.  ...  genes.  ...  If we limit the query to K562, a leukemia cell line, we find two enhancers downstream of the MYC gene (Supplementary Figure S4C ).  ... 
doi:10.1093/nar/gky864 pmid:30247654 pmcid:PMC6323890 fatcat:henwcocizneotot3tawkmj52b4

Downstream E-Box–mediated Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene Transcription: Evidence for an Endogenous Mechanism of Transcriptional Repression

Izumi Horikawa, P. LouAnn Cable, Sharlyn J. Mazur, Ettore Appella, Cynthia A. Afshari, J. Carl Barrett, Elizabeth H. Blackburn
2002 Molecular Biology of the Cell  
Regulation of the hTERT gene encoding the telomerase catalytic subunit plays an important role in human cell senescence, immortalization, and carcinogenesis.  ...  By examining the activity of various deleted or mutated hTERT promoter fragments, we show that an E-box element downstream of the transcription initiation site is critical to differential hTERT transcription  ...  Mitsuo Oshimura and Hiromi Tanaka for chromosomal mapping of the telomerase repressor gene, Dr.  ... 
doi:10.1091/mbc.e01-11-0107 pmid:12181331 pmcid:PMC117927 fatcat:cwfnczup4ng4rbrxmg23ofi3m4

Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene

I Horikawa, P L Cable, C Afshari, J C Barrett
1999 Cancer Research  
The region contains a potential Myc oncoprotein binding site (E-box), and cotransfection of a c-myc expression plasmid markedly enhanced the promoter activity, suggesting a role of the Myc protein in telomerase  ...  Activation of telomerase is one of the rate-limiting steps in human cell immortalization and carcinogenesis Human telomerase is composed of at least two protein subunits and an RNA component.  ...  To investigate a role of c-Myc protein in the hTERT gene transcription (data shown in Fig. 4) , a human c-myc cDNA expression plasmid, RSVmycSVpA (a kind gift from Dr. Chi V.  ... 
pmid:10029071 fatcat:rlb5t5b4djhnjn2cy332rqufxi

Regulatory elements in the immunoglobulin kappa locus induce c-myc activation and the promoter shift in Burkitt's lymphoma cells

A Polack, R Feederle, G Klobeck, K Hörtnagel
1993 EMBO Journal  
The c-myc gene under the control of the complete Ig kappa locus containing matrix attachment region, intron enhancer, constant kappa gene and 3' enhancer was strongly activated with predominant usage of  ...  In the majority of cases the chromosomal breakpoint is localized 3' or 5' of the gene leaving the physiological c-myc transcription unit intact.  ...  Results Sequence and functional identification of the human kappa 3’ enhancer We have shown previously that part of the Ig kappa locus extending from J5 to 2.7 kb 3’ of the constant gene and carrying the  ... 
pmid:8404859 pmcid:PMC413674 fatcat:sxkdhgisxfeqrayhmc6li6bftu

Retroviral insertional mutagenesis: past, present and future

A G Uren, J Kool, A Berns, M van Lohuizen
2005 Oncogene  
Many oncogenes identified in these screens have also been shown to play a causal role in the development of human cancers.  ...  In this review, we discuss the features of retroviral insertion mutagenesis screens, covering the mechanisms by which retroviral insertions mutate cellular genes, the practical aspects of insertion site  ...  Acknowledgements Thanks to Colin Pritchard and Jos Jonkers for critically reading the manuscript and providing helpful suggestions.  ... 
doi:10.1038/sj.onc.1209043 pmid:16299527 fatcat:s45z2i6xtjdjhp5sf56q4xdcbi

Multiple Wnt/ß-Catenin Responsive Enhancers Align with the MYC Promoter through Long-Range Chromatin Loops

Gregory S. Yochum, Mary Bryk
2011 PLoS ONE  
Inappropriate activation of c-Myc (MYC) gene expression by the Wnt/ß-catenin signaling pathway is required for colorectal carcinogenesis.  ...  While each chromatin loop is detected in quiescent cells, the positioning of three of the five distal enhancers with the MYC promoter is induced by serum mitogens.  ...  Faoud Ishmael and Sydney Kyler (Penn State University College of Medicine) for critically reading this manuscript.  ... 
doi:10.1371/journal.pone.0018966 pmid:21533051 pmcid:PMC3080403 fatcat:ytvfdrgge5edhjy7ollmo2jsci
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