1. The Basal Transcription Complex Component TAF3 Transduces Changes in Nuclear Phosphoinositides into Transcriptional Output
- Author
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Stijf-Bultsma, Y., Sommer, L., Tauber, M., Baalbaki, M., Giardoglou, P., Jones, D., Gelato, K., van Pelt, J., Shah, Z., Rahnamoun, H., Toma, C., Anderson, K., Hawkins, P., Lauberth, S., Haramis, A., Hart, D., Fischle, W., and Divecha, N.
- Subjects
Electrophoresis ,Transcription, Genetic ,1.1 Normal biological development and functioning ,Molecular Sequence Data ,Sequence Homology ,Phosphatidylinositols ,Medical and Health Sciences ,Methylation ,Article ,Cell Line ,Histones ,Minor Histocompatibility Antigens ,Myoblasts ,Mice ,Genetic ,Underpinning research ,Genetics ,Animals ,Amino Acid Sequence ,Molecular Biology ,Zebrafish ,Oligonucleotide Array Sequence Analysis ,Cell Nucleus ,Homeodomain Proteins ,TATA-Binding Protein Associated Factors ,Polyacrylamide Gel ,Sequence Homology, Amino Acid ,Gene Expression Profiling ,Lysine ,Phosphotransferases ,Cell Differentiation ,Cell Biology ,Biological Sciences ,Amino Acid ,Phosphotransferases (Alcohol Group Acceptor) ,Mutation ,Electrophoresis, Polyacrylamide Gel ,RNA Interference ,Transcription Factor TFIID ,Transcription ,Developmental Biology ,Protein Binding - Abstract
Summary 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 in vitro and with chromatin in vivo. 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., Graphical Abstract, Highlights • PIP4K2B regulates nuclear PI5P and myogenic gene expression during differentiation • A screen identifies 17 of 32 PHD fingers interacting with phosphoinositides • The basal transcription component TAF3 interacts strongly with phosphoinositides • TAF3 transduces changes in nuclear phosphoinositides into transcriptional output, Bultsma et al. show that the basal transcriptional complex protein TAF3 directly binds phosphoinositides and transduces changes in nuclear phosphoinositides into differential transcriptional output that affects myoblast differentiation. The lipid kinase PIP4K2B, phosphoinositides, and TAF3 form a conserved nuclear signaling pathway that selectively regulates transcription.
- Published
- 2015