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Updated: Jun 14, 2026

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
Published on: September 1, 2019
TEThered to Runx: novel binding partners for runx factors
Xiaodong Li1, Matthew Decker, Jennifer J Westendorf
1Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Abstract:
RUNX transcription factors reside in the nuclear matrix where they integrate numerous signaling pathways to regulate gene expression and affect tissue development, regeneration, and tumorigenesis. An affinity purification and proteomic experiment was performed to identify novel Runx2 binding partners. The interactions between Runx2 and two nuclear factors (Ddx5 and CoAA) identified in this screen were previously described. Coactivator activator (CoAA) bound the DNA binding domain of Runx2 and prevented Runx-driven gene expression. The YxxQ motif in CoAA was required for Runx2 interactions. Members of the FET/TET family of proteins, including FUS/TLS and EWSR1, contain a similar motif and were hypothesized to interact with Runx2. Here, we provide evidence that FUS/TLS, EWSR1, and the Ewing's sarcoma t(12;21) fusion protein EWS-FLI bind Runx2 and alter its transcriptional activity. Potential roles of protein complexes containing FET/TET and RUNX family members during tumor formation and mesenchymal progenitor cell differentiation are discussed.
Insights
RUNX2 interacts with FET/TET proteins, including FUS/TLS and EWSR1, influencing gene expression. These interactions may play roles in cancer development and cell differentiation.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- RUNX transcription factors are key regulators of gene expression, impacting development and disease.
- Nuclear matrix proteins like RUNX2 integrate signaling pathways.
- Previous studies identified Ddx5 and CoAA as Runx2 binding partners.
Purpose of the Study:
- To identify novel Runx2 binding partners.
- To investigate the interaction between Runx2 and FET/TET family proteins.
- To explore the functional consequences of these interactions on transcriptional activity.
Main Methods:
- Affinity purification and proteomic experiments were used to identify binding partners.
- Co-immunoprecipitation assays confirmed interactions.
- Reporter gene assays assessed transcriptional activity.
Main Results:
- FUS/TLS, EWSR1, and the EWS-FLI fusion protein were identified as novel Runx2 binding partners.
- The YxxQ motif, present in CoAA and FET/TET proteins, is crucial for Runx2 interaction.
- Binding of FET/TET proteins to Runx2 altered its transcriptional activity.
Conclusions:
- FET/TET proteins physically interact with Runx2.
- These interactions can modulate Runx2-driven gene expression.
- Protein complexes involving FET/TET and RUNX proteins may be implicated in tumorigenesis and progenitor cell differentiation.
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