EWS and FUS Bind a Subset of Transcribed Genes Encoding Proteins Enriched in RNA Regulatory Functions

Background FUS (TLS) and EWS (EWSR1) belong to the FET-protein family of RNA and DNA binding proteins. FUS and EWS are structurally and functionally related and participate in transcriptional regulation and RNA splicing. FUS and EWS are identified in translocation generated cancer fusion proteins and involved in the human neurological diseases amyotrophic lateral sclerosis and fronto-temporal lobar degeneration. Results To determine the gene regulatory functions of FUS and EWS at the level of chromatin, we have performed Chromatin Immunoprecipitation followed by Next Generation Sequencing (ChIP-Seq). Our results show that FUS and EWS bind to a subset of actively transcribed genes, that binding often is in the 3’ end of genes, and that binding overlaps with RNA polymerase II. Functional examinations of selected target genes verified that FUS and EWS can regulation expression. Gene Ontology (GO) analyses showed that FUS and EWS target genes preferentially encode proteins involved in regulatory processes at the RNA level. Conclusions The presented results yield new insights into gene interactions of EWS and FUS and have identified a set of FUS and EWS target genes involved in pathways at the RNA regulatory level with potential to mediate normal and disease-associated functions of the FUS and EWS proteins. Overall design: To identify the DNA binding profile of FUS, EWS and TAF15 by ChIPseq. Controls: use antibody against H3K9 and input