1. The Basal Transcription Complex Component TAF3 Transduces Changes in Nuclear Phosphoinositides into Transcriptional Output
- Author
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Stijf-Bultsma, Yvette, Sommer, Lilly, Tauber, Maria, Baalbaki, Mai, Giardoglou, Panagiota, Jones, David R, Gelato, Kathy A, van Pelt, Jason, Shah, Zahid, Rahnamoun, Homa, Toma, Clara, Anderson, Karen E, Hawkins, Philip, Lauberth, Shannon M, Haramis, Anna-Pavlina G, Hart, Daniel, Fischle, Wolfgang, and Divecha, Nullin
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Genetics ,Underpinning research ,1.1 Normal biological development and functioning ,Amino Acid Sequence ,Animals ,Cell Differentiation ,Cell Line ,Cell Nucleus ,Electrophoresis ,Polyacrylamide Gel ,Gene Expression Profiling ,Histones ,Homeodomain Proteins ,Lysine ,Methylation ,Mice ,Minor Histocompatibility Antigens ,Molecular Sequence Data ,Mutation ,Myoblasts ,Oligonucleotide Array Sequence Analysis ,Phosphatidylinositols ,Phosphotransferases (Alcohol Group Acceptor) ,Protein Binding ,RNA Interference ,Sequence Homology ,Amino Acid ,TATA-Binding Protein Associated Factors ,Transcription Factor TFIID ,Transcription ,Genetic ,Zebrafish ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - 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 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.
- Published
- 2015