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Transcriptional implications of intragenic DNA methylation in the oestrogen receptor alpha gene in breast cancer cells and tissues

Overview of attention for article published in BMC Cancer, May 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (88th percentile)

Mentioned by

blogs
2 blogs
twitter
3 tweeters
facebook
1 Facebook page

Citations

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14 Dimensions

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43 Mendeley
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Title
Transcriptional implications of intragenic DNA methylation in the oestrogen receptor alpha gene in breast cancer cells and tissues
Published in
BMC Cancer, May 2015
DOI 10.1186/s12885-015-1335-5
Pubmed ID
Authors

Natalie S Shenker, Kirsty J Flower, Charlotte S Wilhelm-Benartzi, Wei Dai, Emma Bell, Edmund Gore, Mona El Bahrawy, Gillian Weaver, Robert Brown, James M Flanagan

Abstract

DNA methylation variability regions (MVRs) across the oestrogen receptor alpha (ESR1) gene have been identified in peripheral blood cells from breast cancer patients and healthy individuals. In contrast to promoter methylation, gene body methylation may be important in maintaining active transcription. This study aimed to assess MVRs in ESR1 in breast cancer cell lines, tumour biopsies and exfoliated epithelial cells from expressed breast milk (EBM), to determine their significance for ESR1 transcription. DNA methylation levels in eight MVRs across ESR1 were assessed by pyrosequencing bisulphite-converted DNA from three oestrogen receptor (ER)-positive and three ER-negative breast cancer cell lines. DNA methylation and expression were assessed following treatment with DAC (1 μM), or DMSO (controls). ESR1 methylation levels were also assayed in DNA from 155 invasive ductal carcinoma biopsies provided by the Breast Cancer Campaign Tissue Bank, and validated with DNA methylation profiles from the TCGA breast tumours (n = 356 ER-pos, n = 109 ER-neg). DNA methylation was profiled in exfoliated breast epithelial cells from EBM using the Illumina 450 K (n = 36) and pyrosequencing in a further 53 donor samples. ESR1 mRNA levels were measured by qRT-PCR. We show that ER-positive cell lines had unmethylated ESR1 promoter regions and highly methylated intragenic regions (median, 80.45%) while ER-negative cells had methylated promoters and lower intragenic methylation levels (median, 38.62%). DAC treatment increased ESR1 expression in ER-negative cells, but significantly reduced methylation and expression of ESR1 in ER-positive cells. The ESR1 promoter was unmethylated in breast tumour biopsies with high levels of intragenic methylation, independent of ER status. However, ESR1 methylation in the strongly ER-positive EBM DNA samples were very similar to ER-positive tumour cell lines. DAC treatment inhibited ESR1 transcription in cells with an unmethylated ESR1 promoter and reduced intragenic DNA methylation. Intragenic methylation levels correlated with ESR1 expression in homogenous cell populations (cell lines and exfoliated primary breast epithelial cells), but not in heterogeneous tumour biopsies, highlighting the significant differences between the in vivo tumour microenvironment and individual homogenous cell types. These findings emphasise the need for care when choosing material for epigenetic research and highlights the presence of aberrant intragenic methylation levels in tumour tissue.

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 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 43 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 21%
Student > Master 8 19%
Student > Bachelor 6 14%
Researcher 4 9%
Student > Doctoral Student 3 7%
Other 6 14%
Unknown 7 16%
Readers by discipline Count As %
Agricultural and Biological Sciences 13 30%
Biochemistry, Genetics and Molecular Biology 10 23%
Medicine and Dentistry 7 16%
Immunology and Microbiology 2 5%
Environmental Science 1 2%
Other 1 2%
Unknown 9 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 14. 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 03 March 2016.
All research outputs
#1,619,648
of 17,356,510 outputs
Outputs from BMC Cancer
#283
of 6,308 outputs
Outputs of similar age
#26,552
of 235,014 outputs
Outputs of similar age from BMC Cancer
#1
of 1 outputs
Altmetric has tracked 17,356,510 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 6,308 research outputs from this source. They receive a mean Attention Score of 4.1. This one has done particularly well, scoring higher than 95% 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 235,014 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 88% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them