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N-Myc Regulates Expression of Pluripotency Genes in Neuroblastoma Including lif, klf2, klf4, and lin28b

Overview of attention for article published in PLOS ONE, June 2009
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Title
N-Myc Regulates Expression of Pluripotency Genes in Neuroblastoma Including lif, klf2, klf4, and lin28b
Published in
PLOS ONE, June 2009
DOI 10.1371/journal.pone.0005799
Pubmed ID
Authors

Rebecca Cotterman, Paul S. Knoepfler

Abstract

myc genes are best known for causing tumors when overexpressed, but recent studies suggest endogenous myc regulates pluripotency and self-renewal of stem cells. For example, N-myc is associated with a number of tumors including neuroblastoma, but also plays a central role in the function of normal neural stem and precursor cells (NSC). Both c- and N-myc also enhance the production of induced pluripotent stem cells (iPSC) and are linked to neural tumor stem cells. The mechanisms by which myc regulates normal and neoplastic stem-related functions remain largely open questions. Here from a global, unbiased search for N-Myc bound genes using ChIP-chip assays in neuroblastoma, we found lif as a putative N-Myc bound gene with a number of strong N-Myc binding peaks in the promoter region enriched for E-boxes. Amongst putative N-Myc target genes in expression microarray studies in neuroblastoma we also found lif and three additional important embryonic stem cell (ESC)-related factors that are linked to production of iPSC: klf2, klf4, and lin28b. To examine the regulation of these genes by N-Myc, we measured their expression using neuroblastoma cells that contain a Tet-regulatable N-myc transgene (TET21N) as well as NSC with a nestin-cre driven N-myc knockout. N-myc levels closely correlated with the expression of all of these genes in neuroblastoma and all but lif in NSC. Direct ChIP assays also indicate that N-Myc directly binds the lif promoter. N-Myc regulates trimethylation of lysine 4 of histone H3 in the promoter of lif and possibly in the promoters of several other stem-related genes. Together these findings indicate that N-Myc regulates overlapping stem-related gene expression programs in neuroblastoma and NSC, supporting a novel model by which amplification of the N-myc gene may drive formation of neuroblastoma. They also suggest mechanisms by which Myc proteins more generally contribute to maintenance of pluripotency and self-renewal of ESC as well as to iPSC formation.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 118 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 <1%
France 1 <1%
Sweden 1 <1%
United Kingdom 1 <1%
Belgium 1 <1%
China 1 <1%
United States 1 <1%
Unknown 111 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 37 31%
Researcher 25 21%
Student > Master 14 12%
Professor > Associate Professor 9 8%
Student > Bachelor 7 6%
Other 12 10%
Unknown 14 12%
Readers by discipline Count As %
Agricultural and Biological Sciences 53 45%
Biochemistry, Genetics and Molecular Biology 20 17%
Medicine and Dentistry 16 14%
Neuroscience 3 3%
Pharmacology, Toxicology and Pharmaceutical Science 2 2%
Other 8 7%
Unknown 16 14%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 September 2013.
All research outputs
#7,429,502
of 22,713,403 outputs
Outputs from PLOS ONE
#88,308
of 193,923 outputs
Outputs of similar age
#38,193
of 113,705 outputs
Outputs of similar age from PLOS ONE
#256
of 507 outputs
Altmetric has tracked 22,713,403 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 193,923 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.0. This one is in the 49th percentile – i.e., 49% of its peers scored the same or lower than it.
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We're also able to compare this research output to 507 others from the same source and published within six weeks on either side of this one. This one is in the 19th percentile – i.e., 19% of its contemporaries scored the same or lower than it.