N-Myc Regulates a Widespread Euchromatic Program in the Human Genome Partially Independent of Its Role as a Classical Transcription Factor

Cotterman, Rebecca; Jin, Victor X.; Krig, Sheryl R.; Lemen, Jessica M.; Wey, Alice; Farnham, Peggy J.; Knoepfler, Paul S.

doi:10.1158/0008-5472.can-08-1961

Cited by 118 publications

(111 citation statements)

References 45 publications

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“…In some cases, this function appears to be important for maintenance of ESC identity, and for the establishment and maintenance of euchromatic chromatin in PSCs by directing H3 and H4 acetylation ( Fig. 2A) (Frank et al 2001;Cotterman et al 2008). Furthermore, transcriptional repression is also an important MYC function unaccounted for by the universal amplifier model.…”

Section: Complexities Of Myc-dependent Transcriptional Regulation In mentioning

confidence: 99%

Roles for MYC in the Establishment and Maintenance of Pluripotency

Chappell

Dalton

2013

Cold Spring Harbor Perspectives in Medicine

100

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MYC and MYCN have been directly implicated in the transcriptional regulation of several thousand genes in pluripotent stem cells and possibly contribute to the activity of all transcribed genes. Control of transcription by a pause-release mechanism, recruitment of positive and negative epigenetic regulators, and a general role in transcriptional amplification have all been implicated as part of the broad, overarching mechanism by which MYC controls stem cell biology. As would be anticipated from the regulation of so many genes, MYC is involved in a wide range of cellular processes including cell-cycle control, metabolism, signal transduction, self-renewal, maintenance of pluripotency, and control of cell fate decisions. MYC transcription factors also have clear roles in cell reprogramming and establishment of the pluripotent state. The mechanism by which MYC accomplishes this is now being explored and promises to uncover unexpected facets of general MYC regulation that are likely to be applicable to cancer biology. In this work we review our current understanding of how MYC contributes to the maintenance and establishment of pluripotent cells and how it contributes to early embryonic development. W ell before MYC was implicated in the establishment and maintenance of pluripotency, it was known as a potent oncogene with roles in transcriptional regulation of metabolism, differentiation, cell lifespan, cell cycle, and cell size control. These functions are all generally relevant to the maintenance and establishment of pluripotent stem cells. Despite this, however, defining the precise mechanism by which MYC functions has been problematic and has led to much confusion. The following discussion will focus on our current understanding of how MYC functions in early embryonic development, maintenance of stem cell identity, and in somatic cell reprogramming. MYC AND MYCN ARE FUNCTIONALLY REDUNDANT IN EARLY EMBRYONIC DEVELOPMENTThe MYC family of basic helix-loop-helix leucine zipper transcription factors consists of MYC, MYCN, and MYCL. DNA binding of MYC family members usually requires heterodimerization with MAX (Myc-associated factor X) through their respective leucine zipper do-

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Section: Complexities Of Myc-dependent Transcriptional Regulation In mentioning

confidence: 99%

Roles for MYC in the Establishment and Maintenance of Pluripotency

Chappell

Dalton

2013

Cold Spring Harbor Perspectives in Medicine

100

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“…MYC-associated factor X is a member of the basic helix-loop-helix leucine zipper family of transcription factor (18). It is able to form the MYC-MAX complex.…”

Section: Discussionmentioning

confidence: 99%

Effects of curcumin on the gene expression profile of L-02 cells

2015

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Abstract. Curcumin has been utilized in the treatment and prevention of disease, including cancer and cardiovascular disease, but the molecular mechanism behind such numerous effects remains unclear. To explore the molecular mechanism and action sites of curcumin at the cellular level, human hepatic L-02 cells were used to assess these effects. Microarray technology was employed to detect the gene expression of L-02 cells treated with curcumin. According to the microarray results and the data from the National Center for Biotechnology Information, the present study classified and concluded that these curcumin-sensitive genes were associated with diseases and their signaling pathway. The study supports the evidence for treating cancer and cardiovascular disease, and found certain potential marker genes for conducting systematic research into the effects of curcumin. A total of 80 genes were identified as significantly differentially expressed between samples treated with and without curcumin. Curcumin is capable of developing physiological reactions and functions by regulating the gene expression and affecting its signal transduction pathway. Tumor protein p63, MYC-associated factor X and certain other genes associated with tumors act on a potential therapeutic target, while apolipoprotein B receptor and oxysterol-binding protein-like 7, and their signaling pathways may be involved in the cardioprotective effects of curcumin.

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“…Myc maintains the undifferentiated state of mESCs at least, in part, through regulating miRNA expression and through its influence on chromatin [16][17][18]. The regulation of chromatin by Myc is surprisingly widespread in both normal stem and tumor cells for a basic-helix-loop-helix-zipper transcription factor [51][52][53][54]. Myc may function in this more global manner on chromatin during the formation of both iPSCs and OF, a possibility being addressed by functional genomics studies on iPSCs.…”

Section: Discussionmentioning

confidence: 99%

Induced Pluripotency and Oncogenic Transformation Are Related Processes

Riggs

Barrilleaux

Varlakhanova

et al. 2013

Stem Cells and Development

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104

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Induced pluripotent stem cells (iPSCs) have the potential for creating patient-specific regenerative medicine therapies, but the links between pluripotency and tumorigenicity raise important safety concerns. More specifically, the methods employed for the production of iPSCs and oncogenic foci (OF), a form of in vitro produced tumor cells, are surprisingly similar, raising potential concerns about iPSCs. To test the hypotheses that iPSCs and OF are related cell types and, more broadly, that the induction of pluripotency and tumorigenicity are related processes, we produced iPSCs and OF in parallel from common parental fibroblasts. When we compared the transcriptomes of these iPSCs and OF to their parental fibroblasts, similar transcriptional changes were observed in both iPSCs and OF. A significant number of genes repressed during the iPSC formation were also repressed in OF, including a large cohort of differentiation-associated genes. iPSCs and OF shared a limited number of genes that were upregulated relative to parental fibroblasts, but gene ontology analysis pointed toward monosaccharide metabolism as upregulated in both iPSCs and OF. iPSCs and OF were distinct in that only iPSCs activated a host of pluripotency-related genes, while OF activated cellular damage and specific metabolic pathways. We reprogrammed oncogenic foci (ROF) to produce iPSC-like cells, a process dependent on Nanog. However, the ROF had reduced differentiation potential compared to iPSC, suggesting that oncogenic transformation leads to cellular changes that impair complete reprogramming. Taken together, these findings support a model in which OF and iPSCs are related, yet distinct cell types, and in which induced pluripotency and induced tumorigenesis are similar processes.

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N-Myc Regulates a Widespread Euchromatic Program in the Human Genome Partially Independent of Its Role as a Classical Transcription Factor

Cited by 118 publications

References 45 publications

Roles for MYC in the Establishment and Maintenance of Pluripotency

Roles for MYC in the Establishment and Maintenance of Pluripotency

Effects of curcumin on the gene expression profile of L-02 cells

Induced Pluripotency and Oncogenic Transformation Are Related Processes

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