Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study shows SNPs associated with breast cancer risk alter binding affinity for pioneer factor FOXA1

24.01.2013
Dartmouth scientists showed that more than half of all the SNPs associated with breast cancer risk are located in distant regions and bound by FOXA1, a protein required for estrogen receptor-á (ER) function according to a paper published in the journal Nature Genetics in November.
Jason Moore, PhD, a Third Century Professor of genetics, director of the Institute for Quantitative Biomedical Sciences, and associate director for bioinformatics at Dartmouth-Hitchcock Norris Cotton Cancer Center, and other researchers used a new methodology that combines cistromics, epigenomics, and genotype imputation to annotate the non-coding regions of the geneomie in breast cancer cells and systematically identify the function nature of SNPS associated with breast cancer risk.

“Understanding the biology behind the genetic risk factors opens the door to identifying new drug targets,” said Dr. Moore.

Results showed that, for breast cancer, the majority of risk-associated SNPs modulate FOXA1 binding. First, they are in complete linkage disequilibrium (LD) with SNPs localized to sites of FOXA1 binding, and, second, these linked SNPs are capable of changing the recruitment of FOXA1 in a significant manner.

Pioneer factors, such as FOXA1, and lineage-specific factors, such as ESR1, underlie the transcriptional programs that establish cell identity. Accordingly, researchers indicated that the majority of SNPs that can disrupt normal breast cell identity modulate the binding of the FOXA1 pioneer factor.

The mechanisms underlying breast cancer risk–associated SNPs are unknown. As with most other complex traits, these risk-associated SNPs map to the non-coding regions of the genome. Researchers demonstrated that breast cancer–associated SNPs are enriched for FOXA1 and ESR1 transcription factor–binding sites and H3K4me1 histone modification. Enrichment is dependent on factor, cell type and cancer type. The body of evidence supporting regulatory mechanisms for GWAS-identified risk-associated SNPs is steadily growing. Heterozygous sites with differential allelic occupancy within 100 bp of transcription start sites have been shown to have a strong association with differential gene expression and to be enriched for GWAS-identified SNPs31. Binding of the FOXA1 pioneer factor is central for chromatin opening and nucleosome positioning favorable to transcription factor recruitment. In addition, FOXA1 is central to the establishment of the transcriptional programs that respond to estrogen stimulation in ESR1-positive breast cancer cells.

This research was funded by the National Institutes of Health (NIH R01M009012 & LM010098).

About Norris Cotton Cancer Center at Dartmouth-Hitchcock

Norris Cotton Cancer Center combines advanced cancer research at Dartmouth College and the Geisel School of Medicine at Dartmouth with patient-centered cancer care provided at Dartmouth-Hitchcock Medical Center, at Dartmouth-Hitchcock regional locations in Manchester, Nashua, and Keene, NH, and St. Johnsbury, VT, and at 12 partner hospitals throughout New Hampshire and Vermont. It is one of 41 centers nationwide to earn the National Cancer Institute’s “Comprehensive Cancer Center” designation. Learn more about Norris Cotton Cancer Center research, programs, and clinical trials online at cancer.dartmouth.edu.

For more information contact Donna Dubuc at (603) 653-3615.

Donna M. Dubuc | EurekAlert!
Further information:
http://www.hitchcock.org

More articles from Health and Medicine:

nachricht Energizing the immune system to eat cancer
22.01.2019 | University of Pennsylvania School of Medicine

nachricht Early Prediction of Alzheimer’s Progression in Blood
22.01.2019 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Bifacial Stem Cells Produce Wood and Bast

Heidelberg researchers study one of the most important growth processes on Earth

So-called bifacial stem cells are responsible for one of the most critical growth processes on Earth – the formation of wood.

Im Focus: Energizing the immune system to eat cancer

Abramson Cancer Center study identifies method of priming macrophages to boost anti-tumor response

Immune cells called macrophages are supposed to serve and protect, but cancer has found ways to put them to sleep. Now researchers at the Abramson Cancer...

Im Focus: Ten-year anniversary of the Neumayer Station III

The scientific and political community alike stress the importance of German Antarctic research

Joint Press Release from the BMBF and AWI

The Antarctic is a frigid continent south of the Antarctic Circle, where researchers are the only inhabitants. Despite the hostile conditions, here the Alfred...

Im Focus: Ultra ultrasound to transform new tech

World first experiments on sensor that may revolutionise everything from medical devices to unmanned vehicles

The new sensor - capable of detecting vibrations of living cells - may revolutionise everything from medical devices to unmanned vehicles.

Im Focus: Flying Optical Cats for Quantum Communication

Dead and alive at the same time? Researchers at the Max Planck Institute of Quantum Optics have implemented Erwin Schrödinger’s paradoxical gedanken experiment employing an entangled atom-light state.

In 1935 Erwin Schrödinger formulated a thought experiment designed to capture the paradoxical nature of quantum physics. The crucial element of this gedanken...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Our digital society in 2040

16.01.2019 | Event News

11th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Aachen, 3-4 April 2019

14.01.2019 | Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

 
Latest News

How our cellular antennas are formed

22.01.2019 | Life Sciences

Proposed engineering method could help make buildings and bridges safer

22.01.2019 | Architecture and Construction

Bifacial Stem Cells Produce Wood and Bast

22.01.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>