title: The basal transcription complex component TAF3 transduces changes in nuclear phosphoinositides into transcriptional output.
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.
authors: The Inositide Laboratory, Centre for Biological Sciences, Highfield Campus, University of Southampton, Southampton SO171BJ, UK; The Inositide Laboratory, the CRUK Manchester Institute, the University of Manchester, Wilmslow Road, Manchester M204BX, UK.
authors: Yvette
authors: Y
authors: Stijf-Bultsma
authors: The Inositide Laboratory, the CRUK Manchester Institute, the University of Manchester, Wilmslow Road, Manchester M204BX, UK.
authors: Lilly
authors: L
authors: Sommer
authors: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
authors: Maria
authors: M
authors: Tauber
authors: University of California, San Francisco, Mail Code 3120, Smith Cardiovascular Research Building, 555 Mission Bay Boulevard, South San Francisco, CA 94158-9001, USA.
authors: Mai
authors: M
authors: Baalbaki
authors: Institute of Biology (IBL), Leiden University, Sylvius Laboratory, Sylviusweg 72, 2333 BE Leiden, the Netherlands.
authors: Panagiota
authors: P
authors: Giardoglou
authors: The Inositide Laboratory, the CRUK Manchester Institute, the University of Manchester, Wilmslow Road, Manchester M204BX, UK.
authors: David R
authors: DR
authors: Jones
authors: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
authors: Kathy A
authors: KA
authors: Gelato
authors: Institute of Biology (IBL), Leiden University, Sylvius Laboratory, Sylviusweg 72, 2333 BE Leiden, the Netherlands.
authors: Jason
authors: J
authors: van Pelt
authors: The Inositide Laboratory, Centre for Biological Sciences, Highfield Campus, University of Southampton, Southampton SO171BJ, UK.
authors: Zahid
authors: Z
authors: Shah
authors: Division of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Homa
authors: H
authors: Rahnamoun
authors: Division of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Clara
authors: C
authors: Toma
authors: Signaling Laboratory, The Babraham Institute, Cambridge, Cambridgeshire CB22 3AT, UK.
authors: Karen E
authors: KE
authors: Anderson
authors: Signaling Laboratory, The Babraham Institute, Cambridge, Cambridgeshire CB22 3AT, UK.
authors: Philip
authors: P
authors: Hawkins
authors: Division of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Shannon M
authors: SM
authors: Lauberth
authors: Institute of Biology (IBL), Leiden University, Sylvius Laboratory, Sylviusweg 72, 2333 BE Leiden, the Netherlands.
authors: Anna-Pavlina G
authors: AP
authors: Haramis
authors: University of California, San Francisco, Mail Code 3120, Smith Cardiovascular Research Building, 555 Mission Bay Boulevard, South San Francisco, CA 94158-9001, USA.
authors: Daniel
authors: D
authors: Hart
authors: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
authors: Wolfgang
authors: W
authors: Fischle
authors: The Inositide Laboratory, Centre for Biological Sciences, Highfield Campus, University of Southampton, Southampton SO171BJ, UK; The Inositide Laboratory, the CRUK Manchester Institute, the University of Manchester, Wilmslow Road, Manchester M204BX, UK. Electronic address: n.divecha@soton.ac.uk.
authors: Nullin
authors: N
authors: Divecha
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D020869:Gene Expression Profiling; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D009154:Mutation; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010716:Phosphatidylinositols / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones; D018398:Homeodomain Proteins; D015778:Minor Histocompatibility Antigens; D010716:Phosphatidylinositols; D035381:TATA-Binding Protein Associated Factors; C532029:Taf3 protein, mouse; D035362:Transcription Factor TFIID; D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase; D008239:Lysine