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Genome‐wide analysis of ETS‐family DNA‐binding in vitro and in vivo
Author(s) -
Wei GongHong,
Badis Gwenael,
Berger Michael F,
Kivioja Teemu,
Palin Kimmo,
Enge Martin,
Bonke Martin,
Jolma Arttu,
Varjosalo Markku,
Gehrke Andrew R,
Yan Jian,
Talukder Shaheynoor,
Turunen Mikko,
Taipale Mikko,
Stunnenberg Hendrik G,
Ukkonen Esko,
Hughes Timothy R,
Bulyk Martha L,
Taipale Jussi
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.106
Subject(s) - biology , chromatin immunoprecipitation , genetics , transcription factor , chip sequencing , dna , dna binding protein , dna binding site , computational biology , chip on chip , binding site , chromatin , dna microarray , plasma protein binding , immunoprecipitation , gene , promoter , microbiology and biotechnology , gene expression , chromatin remodeling
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.