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 van Pelt; Zahid Shah; Homa Rahnamoun; Clara Toma; Karen E Anderson; Philip Hawkins; Shannon M Lauberth; Anna-Pavlina G Haramis; Daniel Hart; Wolfgang Fischle; Nullin Divecha

doi:10.1016/j.molcel.2015.03.009

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

Mol Cell. 2015 May 7;58(3):453-67. doi: 10.1016/j.molcel.2015.03.009. Epub 2015 Apr 9.

Authors

Yvette Stijf-Bultsma¹, Lilly Sommer², Maria Tauber³, Mai Baalbaki⁴, Panagiota Giardoglou⁵, David R Jones², Kathy A Gelato³, Jason van Pelt⁵, Zahid Shah⁶, Homa Rahnamoun⁷, Clara Toma⁷, Karen E Anderson⁸, Philip Hawkins⁸, Shannon M Lauberth⁷, Anna-Pavlina G Haramis⁵, Daniel Hart⁴, Wolfgang Fischle³, Nullin Divecha⁹

Affiliations

¹ 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.
² The Inositide Laboratory, the CRUK Manchester Institute, the University of Manchester, Wilmslow Road, Manchester M204BX, UK.
³ Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
⁴ University of California, San Francisco, Mail Code 3120, Smith Cardiovascular Research Building, 555 Mission Bay Boulevard, South San Francisco, CA 94158-9001, USA.
⁵ Institute of Biology (IBL), Leiden University, Sylvius Laboratory, Sylviusweg 72, 2333 BE Leiden, the Netherlands.
⁶ The Inositide Laboratory, Centre for Biological Sciences, Highfield Campus, University of Southampton, Southampton SO171BJ, UK.
⁷ Division of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA.
⁸ Signaling Laboratory, The Babraham Institute, Cambridge, Cambridgeshire CB22 3AT, UK.
⁹ 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: [email protected].

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Cell Differentiation / genetics
Cell Line
Cell Nucleus / genetics
Cell Nucleus / metabolism*
Electrophoresis, Polyacrylamide Gel
Gene Expression Profiling
Histones / metabolism
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Lysine / metabolism
Methylation
Mice
Minor Histocompatibility Antigens
Molecular Sequence Data
Mutation
Myoblasts / cytology
Myoblasts / metabolism
Oligonucleotide Array Sequence Analysis
Phosphatidylinositols / metabolism*
Phosphotransferases (Alcohol Group Acceptor) / genetics
Phosphotransferases (Alcohol Group Acceptor) / metabolism
Protein Binding
RNA Interference
Sequence Homology, Amino Acid
TATA-Binding Protein Associated Factors
Transcription Factor TFIID / genetics
Transcription Factor TFIID / metabolism
Transcription, Genetic*
Zebrafish / embryology
Zebrafish / genetics
Zebrafish / metabolism

Substances

Histones
Homeodomain Proteins
Minor Histocompatibility Antigens
Phosphatidylinositols
TATA-Binding Protein Associated Factors
Taf3 protein, mouse
Transcription Factor TFIID
Phosphotransferases (Alcohol Group Acceptor)
phosphatidylinositol phosphate 4-kinase
Lysine

Associated data

GEO/GSE66353

Grants and funding

BB/J004456/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom