Journal
EMBO JOURNAL
Volume 29, Issue 13, Pages 2147-2160Publisher
WILEY
DOI: 10.1038/emboj.2010.106
Keywords
cancer; ChIP-seq; DNA-binding specificity; ETS family of transcription factors; transcription factor-DNA binding assay
Categories
Funding
- EU
- Sigrid Juselius Foundation
- Finnish Cancer Organizations
- Biocentrum Helsinki
- Academy of Finland Center of Excellence in Translational Genome-Scale Biology
- Academy of Finland
- NIH/NHGRI [R01 HG003985]
Ask authors/readers for more resources
Members of the large ETS family of transcription factors (TFs) have highly similar DNA-binding domains (DBDs)-yet they have diverse functions and activities in physiology and oncogenesis. Some differences in DNA-binding preferences within this family have been described, but they have not been analysed systematically, and their contributions to targeting remain largely uncharacterized. We report here the DNA-binding profiles for all human and mouse ETS factors, which we generated using two different methods: a high-throughput microwell-based TF DNA-binding specificity assay, and protein-binding microarrays (PBMs). Both approaches reveal that the ETS-binding profiles cluster into four distinct classes, and that all ETS factors linked to cancer, ERG, ETV1, ETV4 and FLI1, fall into just one of these classes. We identify amino-acid residues that are critical for the differences in specificity between all the classes, and confirm the specificities in vivo using chromatin immunoprecipitation followed by sequencing (ChIP-seq) for a member of each class. The results indicate that even relatively small differences in in vitro binding specificity of a TF contribute to site selectivity in vivo. The EMBO Journal (2010) 29, 2147-2160. doi:10.1038/emboj.2010.106; Published online 1 June 2010
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available