Genome-wide analysis of ETS-family DNA-binding in vitro and in vivo

Gong Hong Wei, Gwenael Badis, Michael F. Berger, Teemu Kivioja, Kimmo Palin, Martin Enge, Martin Bonke, Arttu Jolma, Markku Varjosalo, Andrew R. Gehrke, Jian Yan, Shaheynoor Talukder, Mikko Turunen, Mikko Taipale, Hendrik G. Stunnenberg, Esko Ukkonen, Timothy R. Hughes, Martha L. Bulyk, Jussi Taipale

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

430 Citaten (Scopus)

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-2Engels
Pagina's (van-tot)2147-2160
Aantal pagina's14
TijdschriftEMBO Journal
Volume29
Nummer van het tijdschrift13
DOI's
StatusGepubliceerd - 7 jul. 2010
Extern gepubliceerdJa

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