Dishevelled-1 regulates global transcriptomic changes and associates with ETS1 transcription factor.

Area of Science:

• Molecular Biology
• Cellular Signaling
• Epigenetics

Background:

• Dishevelled (DVL) proteins are key regulators in the Wnt-signaling pathway, traditionally known for cytoplasmic functions.
• Recent findings highlight nuclear translocation of DVL, suggesting novel roles in transcriptional and epigenetic regulation.
• The specific transcription factor partners of nuclear DVL1 remain largely uncharacterized.

Purpose of the Study:

• To investigate the genome-wide impact of Dishevelled 1 (DVL1) expression on the transcriptomic landscape.
• To identify transcription factor partners associated with nuclear DVL1.
• To elucidate the mechanisms underlying DVL1's nuclear functions in gene regulation.

Main Methods:

• RNA-sequencing was employed to analyze global transcriptomic changes upon DVL1 modulation.
• Chromatin immunoprecipitation followed by sequencing (ChIP-sequencing) was used to map DVL1 genome-wide binding sites.
• Integration of RNA-sequencing and ChIP-sequencing data identified transcription factor interactions.

Main Results:

• Modulation of DVL1 expression significantly altered the global transcriptomic profile.
• ChIP-sequencing revealed extensive genome-wide binding sites for DVL1.
• Integrated analysis identified ETS1 as a transcription factor binding partner that directs nuclear DVL1 to specific genomic loci.

Conclusions:

• Nuclear DVL1 plays a significant role in transcriptional regulation.
• ETS1 is a novel binding partner for nuclear DVL1, mediating its targeting to specific genomic regions.
• These findings clarify the elusive nuclear functions of DVL1 in gene regulation.