Oh, H., Slattery, M., Ma, L., White, K.P., Mann, R.S., Irvine, K.D. (2014). Yorkie promotes transcription by recruiting a histone methyltransferase complex. Cell Rep. 24(8): 449--459.
FlyBase ID
FBrf0233980
Publication Type
Research paper
Abstract
Hippo signaling limits organ growth by inhibiting the transcriptional coactivator
Yorkie. Despite the key role of Yorkie in both normal and oncogenic growth, the
mechanism by which it activates transcription has not been defined. We report
that Yorkie binding to chromatin correlates with histone H3K4 methylation and is
sufficient to locally increase it. We show that Yorkie can recruit a histone
methyltransferase complex through binding between WW domains of Yorkie and PPxY
sequence motifs of NcoA6, a subunit of the Trithorax-related (Trr)
methyltransferase complex. Cell culture and in vivo assays establish that this
recruitment of NcoA6 contributes to Yorkie's ability to activate transcription.
Mammalian NcoA6, a subunit of Trr-homologous methyltransferase complexes, can
similarly interact with Yorkie's mammalian homolog YAP. Our results implicate
direct recruitment of a histone methyltransferase complex as central to
transcriptional activation by Yorkie, linking the control of cell proliferation
by Hippo signaling to chromatin modification.