Phosphoinositides (PI) are important signaling molecules in the nucleus that influence gene expression. However, if and how nuclear PI directly affects the transcriptional machinery is not known. We report that the lipid kinase PIP4K2B regulates nuclear PI5P and the expression of myogenic genes during myoblast differentiation. A targeted screen for PI interactors identified the PHD finger of TAF3, a TATA box binding protein-associated factor with important roles in transcription regulation, pluripotency, and differentiation. We show that the PI interaction site is distinct from the known H3K4me3 binding region of TAF3 and that PI binding modulates association of TAF3 with H3K4me3 invitro and with chromatin invivo. Analysis of TAF3 mutants indicates that TAF3 transduces PIP4K2B-mediated alterations in PI into changes in specific gene transcription. Our study reveals TAF3 as a direct target of nuclear PI and further illustrates the importance of basal transcription components as signal transducers.
|Original language||English (US)|
|Number of pages||15|
|State||Published - May 7 2015|
Bibliographical noteFunding Information:
We are grateful to the K.W.F. (Netherlands), CRUK (grant no. C5759/A12328), and Southampton University for funding and Prof Timmers (Utrecht University) for reagents and discussion. We would also like to thank colleagues from the Somervaille lab (PICR), the department of biological sciences (U.O.S.) and Y. Yong (PICR) for useful discussions. The work in the lab of W.F. was funded by the Max Planck Society and the Deutsche Forschungsgemeinschaft (grant no. 564967). A.-P.G.H. was funded by the Dutch Cancer Society (KWF) (grant UL 2012-5395). This work was supported in part by the American Cancer Society ACS-IRG #70-002 (S.M.L.). K.A. and P.H. acknowledge support from Biotechnology and Biological Research Council (ISPG BB/J004456/1).
© 2015 The Authors.
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology