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HDAC inhibitors cause site-specific chromatin remodeling at PU.1-bound enhancers in K562 cells

Overview of attention for article published in Epigenetics & Chromatin, April 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (74th percentile)

Mentioned by

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12 tweeters

Citations

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13 Dimensions

Readers on

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39 Mendeley
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1 CiteULike
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Title
HDAC inhibitors cause site-specific chromatin remodeling at PU.1-bound enhancers in K562 cells
Published in
Epigenetics & Chromatin, April 2016
DOI 10.1186/s13072-016-0065-5
Pubmed ID
Authors

Christopher L. Frank, Dinesh Manandhar, Raluca Gordân, Gregory E. Crawford

Abstract

Small molecule inhibitors of histone deacetylases (HDACi) hold promise as anticancer agents for particular malignancies. However, clinical use is often confounded by toxicity, perhaps due to indiscriminate hyperacetylation of cellular proteins. Therefore, elucidating the mechanisms by which HDACi trigger differentiation, cell cycle arrest, or apoptosis of cancer cells could inform development of more targeted therapies. We used the myelogenous leukemia line K562 as a model of HDACi-induced differentiation to investigate chromatin accessibility (DNase-seq) and expression (RNA-seq) changes associated with this process. We identified several thousand specific regulatory elements [~10 % of total DNase I-hypersensitive (DHS) sites] that become significantly more or less accessible with sodium butyrate or suberanilohydroxamic acid treatment. Most of the differential DHS sites display hallmarks of enhancers, including being enriched for non-promoter regions, associating with nearby gene expression changes, and increasing luciferase reporter expression in K562 cells. Differential DHS sites were enriched for key hematopoietic lineage transcription factor motifs, including SPI1 (PU.1), a known pioneer factor. We found PU.1 increases binding at opened DHS sites with HDACi treatment by ChIP-seq, but PU.1 knockdown by shRNA fails to block the chromatin accessibility and expression changes. A machine-learning approach indicates H3K27me3 initially marks PU.1-bound sites that open with HDACi treatment, suggesting these sites are epigenetically poised. We find HDACi treatment of K562 cells results in site-specific chromatin remodeling at epigenetically poised regulatory elements. PU.1 shows evidence of a pioneer role in this process by marking poised enhancers but is not required for transcriptional activation.

Twitter Demographics

The data shown below were collected from the profiles of 12 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 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 3%
United States 1 3%
Italy 1 3%
Unknown 36 92%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 31%
Researcher 7 18%
Student > Bachelor 5 13%
Student > Master 3 8%
Other 2 5%
Other 3 8%
Unknown 7 18%
Readers by discipline Count As %
Agricultural and Biological Sciences 15 38%
Biochemistry, Genetics and Molecular Biology 9 23%
Medicine and Dentistry 4 10%
Immunology and Microbiology 2 5%
Pharmacology, Toxicology and Pharmaceutical Science 2 5%
Other 0 0%
Unknown 7 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 6. 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 19 April 2016.
All research outputs
#1,362,041
of 7,571,218 outputs
Outputs from Epigenetics & Chromatin
#106
of 235 outputs
Outputs of similar age
#61,184
of 244,807 outputs
Outputs of similar age from Epigenetics & Chromatin
#9
of 13 outputs
Altmetric has tracked 7,571,218 research outputs across all sources so far. Compared to these this one has done well and is in the 81st percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 235 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.8. This one has gotten more attention than average, scoring higher than 53% of its peers.
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 244,807 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 74% of its contemporaries.
We're also able to compare this research output to 13 others from the same source and published within six weeks on either side of this one. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.