Samenvatting
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.
Originele taal-2 | Engels |
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Pagina's (van-tot) | 2147-2160 |
Aantal pagina's | 14 |
Tijdschrift | EMBO Journal |
Volume | 29 |
Nummer van het tijdschrift | 13 |
DOI's | |
Status | Gepubliceerd - 7 jul. 2010 |
Extern gepubliceerd | Ja |