Yorkie promotes transcription by recruiting a histone methyltransferase complex

Area of Science:

• Cell Biology
• Molecular Biology
• Epigenetics

Background:

• The Hippo signaling pathway is crucial for regulating organ size by inhibiting the Yorkie transcriptional coactivator.
• The precise mechanism by which Yorkie activates transcription remains largely undefined, despite its role in normal and oncogenic growth.

Purpose of the Study:

• To elucidate the mechanism of transcriptional activation by Yorkie.
• To investigate the link between Yorkie, chromatin modification, and Hippo signaling.

Main Methods:

• Chromatin immunoprecipitation assays to assess Yorkie binding and histone methylation.
• Co-immunoprecipitation to identify protein interactions.
• Cell culture and in vivo assays to validate functional roles.

Main Results:

• Yorkie binding to chromatin correlates with and is sufficient to increase histone H3K4 methylation.
• Yorkie directly recruits the NcoA6 subunit of the Trithorax-related (Trr) methyltransferase complex via its WW domains.
• This recruitment is essential for Yorkie-mediated transcriptional activation and contributes to Hippo pathway's control over cell proliferation.

Conclusions:

• Yorkie directly recruits a histone methyltransferase complex to activate transcription.
• This mechanism links Hippo signaling-controlled cell proliferation to specific chromatin modifications.