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FOXM1 binds directly to non-consensus sequences in the human genome

Overview of attention for article published in Genome Biology, June 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 (80th percentile)

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Title
FOXM1 binds directly to non-consensus sequences in the human genome
Published in
Genome Biology, June 2015
DOI 10.1186/s13059-015-0696-z
Pubmed ID
Authors

Deborah A. Sanders, Michael V. Gormally, Giovanni Marsico, Dario Beraldi, David Tannahill, Shankar Balasubramanian

Abstract

The Forkhead (FKH) transcription factor FOXM1 is a key regulator of the cell cycle and is overexpressed in most types of cancer. FOXM1, similar to other FKH factors, binds to a canonical FKH motif in vitro. However, genome-wide mapping studies in different cell lines have shown a lack of enrichment of the FKH motif, suggesting an alternative mode of chromatin recruitment. We have investigated the role of direct versus indirect DNA binding in FOXM1 recruitment by performing ChIP-seq with wild-type and DNA binding deficient FOXM1. An in vitro fluorescence polarization assay identified point mutations in the DNA binding domain of FOXM1 that inhibit binding to a FKH consensus sequence. Cell lines expressing either wild-type or DNA binding deficient GFP-tagged FOXM1 were used for genome-wide mapping studies comparing the distribution of the DNA binding deficient protein to the wild-type. This shows that interaction of the FOXM1 DNA binding domain with target DNA is essential for recruitment. Moreover, analysis of the protein interactome of wild-type versus DNA binding deficient FOXM1 shows that the reduced recruitment is not due to inhibition of protein-protein interactions. A functional DNA binding domain is essential for FOXM1 chromatin recruitment. Even in FOXM1 mutants with almost complete loss of binding, the protein-protein interactions and pattern of phosphorylation are largely unaffected. These results strongly support a model whereby FOXM1 is specifically recruited to chromatin through co-factor interactions by binding directly to non-canonical DNA sequences.

X Demographics

X Demographics

The data shown below were collected from the profiles of 15 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 77 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 1%
Netherlands 1 1%
France 1 1%
Germany 1 1%
Unknown 73 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 24 31%
Researcher 15 19%
Student > Master 6 8%
Professor > Associate Professor 5 6%
Student > Bachelor 4 5%
Other 13 17%
Unknown 10 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 29 38%
Agricultural and Biological Sciences 22 29%
Chemistry 4 5%
Medicine and Dentistry 2 3%
Computer Science 2 3%
Other 4 5%
Unknown 14 18%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 8. 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 10 September 2015.
All research outputs
#4,652,510
of 25,374,917 outputs
Outputs from Genome Biology
#2,744
of 4,467 outputs
Outputs of similar age
#53,806
of 278,312 outputs
Outputs of similar age from Genome Biology
#48
of 67 outputs
Altmetric has tracked 25,374,917 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 4,467 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 27.6. This one is in the 38th percentile – i.e., 38% 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 278,312 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 80% of its contemporaries.
We're also able to compare this research output to 67 others from the same source and published within six weeks on either side of this one. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.