EWS and FUS bind a subset of transcribed genes encoding proteins enriched in RNA regulatory functions

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 processing. FUS and EWS are identified in translocation generated cancer fusion proteins and involve...

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Published in:BMC genomics 2015-11, Vol.16 (934), p.929-929, Article 929
Main Authors: Luo, Yonglun, Blechingberg, Jenny, Fernandes, Ana Miguel, Li, Shengting, Fryland, Tue, Børglum, Anders D, Bolund, Lars, Nielsen, Anders Lade
Format: Article
Language:English
Subjects:
Amyotrophic lateral sclerosis
Analysis
Care and treatment
Chromatin - metabolism
Chromatin Immunoprecipitation
Complications and side effects
DNA binding proteins
Genetic transcription
Genomics
HEK293 Cells
Humans
Influence
Protein Binding
RNA - genetics
RNA Processing, Post-Transcriptional
RNA-Binding Protein EWS - metabolism
RNA-Binding Protein FUS - metabolism
Transcription, Genetic
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Summary: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 processing. 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. 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 downstream the poly(A)-signal, and that binding overlaps with RNA polymerase II. Functional examinations of selected target genes identified that FUS and EWS can regulate gene expression at different levels. Gene Ontology analyses showed that FUS and EWS target genes preferentially encode proteins involved in regulatory processes at the RNA level. 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.
ISSN:1471-2164
1471-2164
DOI:10.1186/s12864-015-2125-9