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Genome-wide co-occupancy of AML1-ETO and N-CoR defines the t(8;21) AML signature in leukemic cells

Overview of attention for article published in BMC Genomics, April 2015
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  • Above-average Attention Score compared to outputs of the same age (55th percentile)

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3 tweeters

Citations

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26 Dimensions

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26 Mendeley
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Title
Genome-wide co-occupancy of AML1-ETO and N-CoR defines the t(8;21) AML signature in leukemic cells
Published in
BMC Genomics, April 2015
DOI 10.1186/s12864-015-1445-0
Pubmed ID
Authors

Daniel J Trombly, Troy W Whitfield, Srivatsan Padmanabhan, Jonathan AR Gordon, Jane B Lian, Andre J van Wijnen, Sayyed K Zaidi, Janet L Stein, Gary S Stein

Abstract

Many leukemias result from chromosomal rearrangements. The t(8;21) chromosomal translocation produces AML1-ETO, an oncogenic fusion protein that compromises the function of AML1, a transcription factor critical for myeloid cell differentiation. Because of the pressing need for new therapies in the treatment of acute myleoid leukemia, we investigated the genome-wide occupancy of AML1-ETO in leukemic cells to discover novel regulatory mechanisms involving AML-ETO bound genes. We report the co-localization of AML1-ETO with the N-CoR co-repressor to be primarily on genomic regions distal to transcriptional start sites (TSSs). These regions exhibit over-representation of the motif for PU.1, a key hematopoietic regulator and member of the ETS family of transcription factors. A significant discovery of our study is that genes co-occupied by AML1-ETO and N-CoR (e.g., TYROBP and LAPTM5) are associated with the leukemic phenotype, as determined by analyses of gene ontology and by the observation that these genes are predominantly up-regulated upon AML1-ETO depletion. In contrast, the AML1-ETO/p300 gene network is less responsive to AML1-ETO depletion and less associated with the differentiation block characteristic of leukemic cells. Furthermore, a substantial fraction of AML1-ETO/p300 co-localization occurs near TSSs in promoter regions associated with transcriptionally active loci. Our findings establish a novel and dominant t(8;21) AML leukemia signature characterized by occupancy of AML1-ETO/N-CoR at promoter-distal genomic regions enriched in motifs for myeloid differentiation factors, thus providing mechanistic insight into the leukemic phenotype.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 26 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 42%
Researcher 4 15%
Student > Doctoral Student 3 12%
Professor 2 8%
Student > Bachelor 1 4%
Other 2 8%
Unknown 3 12%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 35%
Agricultural and Biological Sciences 6 23%
Medicine and Dentistry 3 12%
Chemistry 2 8%
Sports and Recreations 1 4%
Other 1 4%
Unknown 4 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 28 January 2016.
All research outputs
#2,986,404
of 7,059,888 outputs
Outputs from BMC Genomics
#2,636
of 5,325 outputs
Outputs of similar age
#89,881
of 212,190 outputs
Outputs of similar age from BMC Genomics
#161
of 246 outputs
Altmetric has tracked 7,059,888 research outputs across all sources so far. This one has received more attention than most of these and is in the 56th percentile.
So far Altmetric has tracked 5,325 research outputs from this source. They receive a mean Attention Score of 4.0. This one is in the 47th percentile – i.e., 47% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 212,190 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.
We're also able to compare this research output to 246 others from the same source and published within six weeks on either side of this one. This one is in the 29th percentile – i.e., 29% of its contemporaries scored the same or lower than it.