
EWSR1::FLI1 융합 단백질의 DBD-α4 나선은 GGAA 마이크로 위성에 대한 협력적 결합을 촉진하여 Ewing 육종 세포에서 TAD 형성, 크로마틴 루프, 증강제 및 생산적인 전사 허브 형성과 같은 유전체 조절 측면을 뒷받침한다.


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Ewing sarcoma is the second most common bone cancer in children and young adults. In 85% of patients, a translocation between chromosomes 11 and 22 results in a potent fusion oncoprotein, EWSR1::FLI1. EWSR1::FLI1 is the only genetic alteration in an otherwise unaltered genome of Ewing sarcoma tumors. The EWSR1 portion of the protein is an intrinsically disordered domain involved in transcriptional regulation by EWSR1::FLI1. The FLI portion of the fusion contains a DNA binding domain shown to bind core GGAA motifs and GGAA repeats. A small alpha-helix in the DNA binding domain of FLI1, DBD-α4 helix, is critical for the transcription function of EWSR1::FLI1. In this study, we aimed to understand the mechanism by which the DBD-α4 helix promotes transcription, and therefore oncogenic transformation. We utilized a multi-omics approach to assess chromatin organization, active chromatin marks, genome binding, and gene expression in cells expressing EWSR1::FLI1 constructs with and without the DBD-α4 helix. Our studies revealed DBD-α4 helix is crucial for cooperative binding of EWSR1::FLI1 at GGAA microsatellites. This binding underlies many aspects of genome regulation by EWSR1::FLI1 such as formation of TADs, chromatin loops, enhancers and productive transcription hubs.

### Competing Interest Statement

The authors have declared no competing interest.

The DBD-α4 helix of EWSR1::FLI1 is required for GGAA microsatellite binding that underlies genome regulation in Ewing sarcoma

ewsr1-fli1-융합-단백질의-dbd-α4-나선이-ewing-육종-유전체-조절에-필수적인-ggaa-마이크로-위성-결합을-위해-필요하다


EWSR1::FLI1 융합 단백질의 DBD-α4 나선이 Ewing 육종 유전체 조절에 필수적인 GGAA 마이크로 위성 결합을 위해 필요하다
