PMID- 22308434 OWN - NLM STAT- MEDLINE DCOM- 20120330 LR - 20211021 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 109 IP - 6 DP - 2012 Feb 7 TI - Ecotopic viral integration site 1 (EVI1) regulates multiple cellular processes important for cancer and is a synergistic partner for FOS protein in invasive tumors. PG - 2168-73 LID - 10.1073/pnas.1119229109 [doi] AB - Ecotropic viral integration site 1 (EVI1) is an oncogenic dual domain zinc finger transcription factor that plays an essential role in the regulation of hematopoietic stem cell renewal, and its overexpression in myeloid leukemia and epithelial cancers is associated with poor patient survival. Despite the discovery of EVI1 in 1988 and its emerging role as a dominant oncogene in various types of cancer, few EVI1 target genes are known. This lack of knowledge has precluded a clear understanding of exactly how EVI1 contributes to cancer. Using a combination of ChIP-Seq and microarray studies in human ovarian carcinoma cells, we show that the two zinc finger domains of EVI1 bind to DNA independently and regulate different sets of target genes. Strikingly, an enriched fraction of EVI1 target genes are cancer genes or genes associated with cancer. We also show that more than 25% of EVI1-occupied genes contain linked EVI1 and activator protein (AP)1 DNA binding sites, and this finding provides evidence for a synergistic cooperative interaction between EVI1 and the AP1 family member FOS in the regulation of cell adhesion, proliferation, and colony formation. An increased number of dual EVI1/AP1 target genes are also differentially regulated in late-stage ovarian carcinomas, further confirming the importance of the functional cooperation between EVI1 and FOS. Collectively, our data indicate that EVI1 is a multipurpose transcription factor that synergizes with FOS in invasive tumors. FAU - Bard-Chapeau, Emilie A AU - Bard-Chapeau EA AD - Institute of Molecular and Cell Biology, Singapore 138673. FAU - Jeyakani, Justin AU - Jeyakani J FAU - Kok, Chung H AU - Kok CH FAU - Muller, Julius AU - Muller J FAU - Chua, Belinda Q AU - Chua BQ FAU - Gunaratne, Jayantha AU - Gunaratne J FAU - Batagov, Arsen AU - Batagov A FAU - Jenjaroenpun, Piroon AU - Jenjaroenpun P FAU - Kuznetsov, Vladimir A AU - Kuznetsov VA FAU - Wei, Chia-Lin AU - Wei CL FAU - D'Andrea, Richard J AU - D'Andrea RJ FAU - Bourque, Guillaume AU - Bourque G FAU - Jenkins, Nancy A AU - Jenkins NA FAU - Copeland, Neal G AU - Copeland NG LA - eng SI - GEO/GSE25210 SI - GEO/GSE25212 SI - GEO/GSE25213 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120119 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (DNA-Binding Proteins) RN - 0 (MDS1 and EVI1 Complex Locus Protein) RN - 0 (MECOM protein, human) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (Transcription Factors) RN - 9007-49-2 (DNA) SB - IM MH - Binding Sites MH - Cell Adhesion MH - Chromatin Immunoprecipitation MH - DNA/genetics/metabolism MH - DNA-Binding Proteins/*metabolism MH - Epithelial Cells/metabolism/pathology MH - Gene Expression Regulation MH - HeLa Cells MH - Humans MH - MDS1 and EVI1 Complex Locus Protein MH - Neoplasm Invasiveness MH - Neoplasms/*metabolism/*pathology MH - Protein Binding MH - Proto-Oncogene Proteins c-fos/*metabolism MH - Proto-Oncogenes MH - Transcription Factors/*metabolism PMC - PMC3277513 COIS- The authors declare no conflict of interest. EDAT- 2012/02/07 06:00 MHDA- 2012/03/31 06:00 PMCR- 2012/08/07 CRDT- 2012/02/07 06:00 PHST- 2012/02/07 06:00 [entrez] PHST- 2012/02/07 06:00 [pubmed] PHST- 2012/03/31 06:00 [medline] PHST- 2012/08/07 00:00 [pmc-release] AID - 1119229109 [pii] AID - 201119229 [pii] AID - 10.1073/pnas.1119229109 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):2168-73. doi: 10.1073/pnas.1119229109. Epub 2012 Jan 19.