The basal transcription complex component TAF3 transduces changes in nuclear phosphoinositides into transcriptional output

Yvette Stijf-Bultsma, Lilly Sommer, Maria Tauber, Mai Baalbaki, Panagiota Giardoglou, David R. Jones, Kathy A. Gelato, Jason vanPelt, Zahid Shah, Homa Rahnamoun, Clara Toma, Karen E. Anderson, Philip Hawkins, Shannon M. Lauberth, Anna Pavlina G. Haramis, Daniel Hart, Wolfgang Fischle, Nullin Divecha*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)453-467
Number of pages15
JournalMolecular Cell
Volume58
Issue number3
DOIs
StatePublished - May 7 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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